European Journal Of Clinical Pharmacology[JOURNAL]
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200 papers
Olanzapine for chemotherapy-induced nausea and vomiting in breast cancer: a systematic review and meta-analysis of prospective randomised controlled trials.
Jafri SM, Shah MS, Nawaz J … +4 more , Siddiqui ZA, Faisal M, Mir AK, Jamal RT
Eur J Clin Pharmacol · 2026 Jun · PMID 42295427 · Publisher ↗
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for breast cancer patients receiving highly emetogenic chemotherapy despite routine antiemetic practice. In this systematic review an...
PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem for breast cancer patients receiving highly emetogenic chemotherapy despite routine antiemetic practice. In this systematic review and meta-analysis we aim to examine the efficacy and safety of olanzapine with regular antiemetic treatment for CINV prevention in breast cancer patients. METHODS: Following PRISMA 2020 standards, we searched PubMed, Cochrane Library, Google scholar, and ClinicalTrials.gov. We retrieved RCTs exclusively, comparing olanzapine with placebo or routine care in breast cancer patients undergoing anthracycline-based chemotherapy. The protocol was registered to PROSPERO (CRD420251087309). The primary outcomes assessed were complete response (defined as no emesis and no rescue medication use) and total control (defined as no nausea, no emesis, and no rescue medication use). Certainty of evidence was assessed using the GRADE approach. RESULTS: Four RCTs involving 857 patients were included. Compared with placebo or standard antiemetic therapy alone, olanzapine significantly improved complete response rates (4 studies, 857 patients; RR 1.58, 95% CI 1.35-1.85; I² = 0%) and total control (2 studies, 600 patients; RR 1.93, 95% CI 1.49-2.50; I² = 0%). Subgroup analysis showed no statistically significant difference between 5 mg and 10 mg doses. Olanzapine decreased acute nausea (3 studies, 377 patients; RR 1.32, 95% CI 1.03-1.69, I² = 63.4%) and delayed nausea (3 studies, 377 patients; RR 1.22, 95% CI 1.06-1.41, I² = 0%). The overall impact on nausea control was not statistically significant and showed considerable heterogeneity (3 studies, 377 patients; RR 1.42, 95% CI 0.48-4.15; I² = 88.0%). Subgroup analysis showed no statistically significant difference between 5 mg and 10 mg doses. Side effects, including sedation, fatigue, sleeplessness, extrapyramidal symptoms, and increased appetite were significantly attributable to olanzapine. GRADE assessment showed low certainty evidence for complete response, total control, and delayed nausea outcomes, while evidence for acute complete response, acute nausea control, and overall nausea control was rated very low certainty due to risk of bias, inconsistency, and imprecision. CONCLUSION: Olanzapine significantly enhances CINV prevention in breast cancer patients, with positive outcomes for both 5 mg and 10 mg doses. Although increased sedation occurred, it was generally well-tolerated.
Comment on "pharmacogenomics-guided treatment versus conventional treatment in patients with schizophrenia: evaluation of medication adherence and switching rate".
Shaik MR, Kamath A
Eur J Clin Pharmacol · 2026 Jun · PMID 42286368 · Publisher ↗
Abstract loading — click title to view on PubMed.
Population pharmacokinetics of unbound imipenem in critically ill patients: a comparison of five renal function estimators for PK/PD-guided dosing.
Boonpeng A, Jaruratanasirikul S, Jullangkoon M … +1 more , Samaeng M
Eur J Clin Pharmacol · 2026 Jun · PMID 42274818 · Publisher ↗
BACKGROUND: Optimizing imipenem therapy in intensive care patients presents challenges due to pathophysiological changes affecting drug disposition. This study developed a population pharmacokinetics model, determined op...
BACKGROUND: Optimizing imipenem therapy in intensive care patients presents challenges due to pathophysiological changes affecting drug disposition. This study developed a population pharmacokinetics model, determined optimal dosing strategies, and described the observed pharmacokinetic/pharmacodynamic (PK/PD) target attainment and clinical outcomes. METHODS: Critically ill patients receiving imipenem/cilastatin were enrolled prospectively. Five blood samples per patient were collected within 24-48 h of treatment initiation. Nonlinear mixed-effects modeling characterized drug pharmacokinetics, with Monte Carlo simulations assessing target attainment probabilities. RESULTS: The study enrolled 21 critically ill patients. A two-compartment model with first-order elimination optimally described imipenem pharmacokinetics, with estimated parameters including total clearance (8.75 L/h), intercompartmental clearance (15.9 L/h), central volume (15.2 L), and peripheral volume (23.4 L). Among evaluated covariates, only estimated glomerular filtration rate (using CKD-EPI 2021 equation) significantly influenced drug clearance. Probability of target attainment analysis (PTA) demonstrated that conventional dosing regimens provided ≥ 90% probability of achieving 40% free time above MIC (fT > MIC) for organisms with MIC values ≤ 2 mg/L. Achieving 75% fT > MIC required maximum conventional doses, whereas 100% fT > MIC with adequate PTA (≥ 80%) necessitated continuous infusion strategies employing doses 30-50% above standard recommendations. Clinical success was observed in 23% of patients (3/13), with higher fT > MIC values among successful cases. However, treatment failure still occurred in some patients despite achieving 100% fT > MIC, suggesting multifactorial determinants of outcomes in critically ill patients. CONCLUSION: Renal function significantly influences imipenem clearance. While standard dosing provides sufficient coverage for conventional PK/PD targets, continuous infusions should be considered for more aggressive targets.
Prognostic relevance of β1-adrenergic receptor polymorphisms on cardiovascular outcome in patients treated with metoprolol after acute myocardial infarction - an observational study.
Bruun LD, Andersen GØ, Myhre PL … +5 more , Halvorsen S, Kringen MK, Hansen CH, Molden E, Øie E
Eur J Clin Pharmacol · 2026 Jun · PMID 42271119 · Full text
PURPOSE: To investigate the association between β1-adrenergic receptor (ADRB1) polymorphisms on cardiovascular events in patients treated with metoprolol after acute myocardial infarction (AMI). METHODS: Patients hospita...
PURPOSE: To investigate the association between β1-adrenergic receptor (ADRB1) polymorphisms on cardiovascular events in patients treated with metoprolol after acute myocardial infarction (AMI). METHODS: Patients hospitalized for AMI (n = 1584) who were treated with metoprolol at discharge were genotyped for the ADRB1 variants Arg389Gly and Ser49Gly. The association between the ADRB1 variants and major adverse cardiovascular events (MACE) and cardiovascular death were assessed by the Cox proportional hazards model, using both a dominant and a codominant genetic model, as well as by haplotype copy number. RESULTS: After three years of follow-up, MACE occurred in 105 and cardiovascular death in 47 patients. Gly389 homozygotes (n = 105, 11 events; hazard ratio [HR] 2.02 [1.01, 4.02], p = 0.046), but not heterozygotes (n = 588, 45 events, HR 1.40 [0.90, 2.13], p = 0.12) were at increased risk of MACE, compared with Arg389 homozygotes (n = 891, 49 events). The risk was not significantly different when all Gly389 carriers were merged (p = 0.052). No primary events occurred in Gly49 homozygotes (n = 28); however, when merged with Gly49 heterozygous carriers (n = 383, 6 events) we found a numerical, but not statistically significant difference in cardiovascular deaths relative to Ser49 homozygotes (n = 1173, 41 events) (p = 0.07). The Arg389Ser49 haplotype was not associated with a primary outcome. CONCLUSION: In post-AMI patients treated with metoprolol, Gly389 homozygotes, but not heterozygotes were associated with an increased risk of MACE compared with Arg389 homozygotes. Our observations raise the possibility of a protective association of the Gly49 variant on cardiovascular death, but this hypothesis requires validation in larger, future studies.
Comparative efficacy and safety of carboplatin-based versus cisplatin-based chemotherapy in muscle-invasive and advanced bladder cancer: A systematic review and meta-analysis.
Liao J, Li X, Li G
Eur J Clin Pharmacol · 2026 Jun · PMID 42271082 · Publisher ↗
BACKGROUND: Cisplatin-based chemotherapy is the standard of care for muscle-invasive and advanced bladder cancer, but its significant toxicity renders approximately 30-50% of patient ineligible. Carboplatin is widely use...
BACKGROUND: Cisplatin-based chemotherapy is the standard of care for muscle-invasive and advanced bladder cancer, but its significant toxicity renders approximately 30-50% of patient ineligible. Carboplatin is widely used as a substitute; however, its comparative efficacy and safety remain controversial due to fragmented and inconsistent evidence. This meta-analysis aims to compare survival outcomes, response rates, and toxicity profiles between carboplatin- and cisplatin-based regimens. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines (PROSPERO: CRD420251249371). MEDLINE, Embase, Cochrane Library, and Web of Science were searched from inception to December 2025 for studies comparing carboplatin-based versus cisplatin-based chemotherapy and restricting study populations to patients with bladder cancer only. This strict selection criterion was applied intentionally to ensure homogeneity. Outcomes included overall survival (OS), cancer-specific survival (CSS), objective response rate (ORR), pathological complete response (pCR) and adverse events (AEs). Risk of bias was assessed using RoB 2 (RCTs) and ROBINS-I (observational studies). Data were pooled using random-effects models. Heterogeneity was quantified using I² statistics. RESULTS: Eleven studies (2 RCTs, 9 cohort studies; n = 2,543 patients) were included. Compared to cisplatin-based regimens, carboplatin-based regimens were associated with worse OS (HR = 1.30, 95% CI: 1.11-1.52; I² = 47%) and CSS (HR = 1.79, 95% CI: 1.39-2.32; I² = 16%). This survival disadvantage was pronounced in palliative settings (OS: HR = 1.27; 95% CI, 1.08-1.50; I² = 0%; CSS: HR = 1.79; 95% CI, 1.16-2.77; I² = 0%) but not significant in neoadjuvant settings (OS: HR = 1.15; 95% CI, 0.97-1.37; I² = 26%; CSS: HR = 1.86; 95% CI, 0.93-3.69; I² = 70%; pCR: RR = 0.92; 95% CI, 0.70-1.22; I² = 0%). Carboplatin is associated with significantly lower gastrointestinal toxicity (RR = 0.30; 95% CI, 0.15-0.62; I² = 0%). No significant differences were observed in hematologic toxicity (RR = 1.27; 95% CI, 0.37-4.30; I² = 75%) or grade 3-4 adverse events (RR = 0.61; 95% CI, 0.24-1.55; I² = 87%). CONCLUSIONS: Based largely on observational studies, this study suggests that cisplatin is associated with better survival than carboplatin in bladder cancer, particularly in palliative setting. In the neoadjuvant setting, no significant difference was found while this does not imply equivalence. Carboplatin offers lower gastrointestinal toxicity and remains an option for cisplatin-ineligible patients. However, our strict selection excluded pivotal studies enrolling mixed urothelial carcinoma limits generalizability to the broader urothelial cancer population. A less strict selection that included such studies might alter effect estimates. Future RCTs with broader inclusion criteria are needed to confirm our findings.
Efficacy of NEPA for prevention of chemotherapy induced nausea and vomiting in head and neck cancer patients receiving cisplatin-based chemotherapy.
Hwang TZ, Wang CC, Yang CC … +6 more , Lien CF, Wang CC, Shih YC, Yeh SA, Yeh TH, Hsieh MC
Eur J Clin Pharmacol · 2026 Jun · PMID 42268415 · Publisher ↗
BACKGROUND: A 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) in combination with a neurokinin-1 receptor antagonist (NK-1RA) are effective for the prevention of chemotherapy induced nausea and vomiting. OBJECTIVES:...
BACKGROUND: A 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) in combination with a neurokinin-1 receptor antagonist (NK-1RA) are effective for the prevention of chemotherapy induced nausea and vomiting. OBJECTIVES: We investigated the efficacy between oral netupitant and palonosetron (NEPA) and intravenous fosaprepitant and palonosetron (FOPA) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients treated with cisplatin-based chemotherapy. METHODS: R/M HNSCC patients who were treated with cisplatin-based chemotherapy as first-line treatment were enrolled in our study. All patients were stratified according to anti-emetic agents, classifying into NEPA group and FOPA group. Anti-emetic efficacy, patients self-report scores and hospitalization days were compared between NEPA and FOPA. RESULTS: A total of 425 R/M HNSCC patients were recruited into our study, with 211 patients in NEPA and 214 patients in FOPA. Anti-emetic efficacy were all significantly better with NEPA than with FOPA across cycle 1 to 5. The mean nausea score were 2.9 vs. 3.4 (p = 0.004) and the mean vomiting score were 1.4 vs. 2.7 (P = 0.001) in cycle 1 for NEPA group and FOPA group, respectively. The mean satisfaction scores were 8.5 vs. 8.2 ( P = 0.032) in cycle1 for NEPA group and FOPA group, respectively. Furthermore, the mean hospitalization days were shorter in NEPA than those in FOPA across cycle 1 to 5, with mean hospitalization days 6.0 versus 7.0 days in cycle 1, respectively. CONCLUSIONS: Oral NEPA exhibited a superior anti-emetic efficacy than intravenous FOPA, as well as shorter hospitalization days for R/M HNSCC patients treated with cisplatin-based chemotherapy.
SGLT2 inhibitors and incretin-based therapies for metabolic dysfunction-associated steatohepatitis: a systematic review.
Cruz AM, Lima BCV, de Ferreira JESM … +1 more , Teles RB
Eur J Clin Pharmacol · 2026 Jun · PMID 42265474 · Full text
BACKGROUND: In recent years, metabolic therapies originally developed to treat systemic metabolic disorders have been investigated as potential therapeutic strategies for Metabolic dysfunction-associated steatohepatitis...
BACKGROUND: In recent years, metabolic therapies originally developed to treat systemic metabolic disorders have been investigated as potential therapeutic strategies for Metabolic dysfunction-associated steatohepatitis (MASH). OBJECTIVE: This study aimed to critically evaluate recent clinical evidence on emerging metabolic therapies, particularly sodium-glucose cotransporter-2 (SGLT2) inhibitors and incretin-based agents, examining their effects on hepatic and metabolic outcomes and, when available, histological endpoints, as well as safety in patients with MASH. METHODS: A systematic review of clinical studies evaluating metabolic therapies in patients with MASH or metabolically associated fatty liver disease was conducted. Randomized clinical trials and other relevant clinical studies investigating SGLT2 inhibitors, incretin-based therapies, and other emerging metabolic agents were included. Outcomes of interest comprised metabolic parameters, hepatic outcomes related to steatosis and disease activity, and histological endpoints when available. RESULTS: Twelve clinical studies were included. In trials with histological endpoints, semaglutide achieved steatohepatitis resolution without worsening of fibrosis in 62.9% versus 34.3% with placebo in a phase 3 trial (p < 0.001), while a phase 2 trial reported NASH resolution in 59% versus 17% with placebo (p < 0.001), without significant fibrosis improvement (43% versus 33%; p = 0.48). Tirzepatide achieved MASH resolution without worsening of fibrosis in 44-62% of patients versus 10% with placebo (p < 0.001 for all doses), and fibrosis improvement in 51-55% versus 30%. Among SGLT2 inhibitors, dapagliflozin achieved MASH improvement without worsening of fibrosis in 53% versus 30% (p = 0.006), MASH resolution in 23% versus 8% (p = 0.01), and fibrosis improvement in 45% versus 20% (p = 0.001). Overall, metabolic therapies improved body weight, hepatic steatosis, glycemic parameters, and disease activity, but evidence for durable fibrosis regression and long-term liver-related outcomes remains heterogeneous. CONCLUSION: Emerging metabolic therapies show promising effects on metabolic and hepatic outcomes in patients with MASH. Incretin-based therapies appear to exert particularly robust effects on body weight reduction and steatohepatitis resolution, whereas SGLT2 inhibitors may provide complementary metabolic, cardiometabolic, and hepatic benefits. Nevertheless, fibrosis-related effects remain less consistent across studies, and future trials with paired histological endpoints, longer follow-up, and clinically meaningful liver-related outcomes are needed.
From authorisation to clinical practice: evolution of the use of biological medicines according to the SmPC and guidelines (2006 to 2025).
Penninx BMF, Hollak CEM, Tas SW … +3 more , Timmers L, de Visser SJ, van Kempen ZLE
Eur J Clin Pharmacol · 2026 Jun · PMID 42265224 · Full text
PURPOSE: After the marketing authorisation of biologicals, uncertainty often remains regarding their real-world effectiveness, safety, and rational use. This study investigates how frequently the recommended use of biolo...
PURPOSE: After the marketing authorisation of biologicals, uncertainty often remains regarding their real-world effectiveness, safety, and rational use. This study investigates how frequently the recommended use of biologicals changes post-authorisation, and who funds the studies leading to these changes. METHODS: Biologicals receiving a positive opinion for adult indications by the Committee for Medicinal Products for Human use (CHMP) between 2006 and 2010 were identified. For each indication, we compared the initial and current Summary of Product Characteristics (SmPC), as well as current SmPC and European clinical guidelines, to identify discrepancies in start and stop criteria, dosage, and administration frequency. We assessed whether discrepancies led to increased or decreased use of the biological and whether this was associated with the sponsor type of supporting publications. FINDINGS: SmPC changes, driven by Marketing Authorisation Holder (MAH)-sponsored studies, were found in 47% of identified indication-biological combinations: 41% led to increased use, 29% to decreased use, and 29% were neutral. Guideline-SmPC discrepancies, mostly supported by publicly sponsored studies, were identified in 75% of cases, with most discrepancies (86%) recommending decreased use. Publications sponsored by public healthcare stakeholders were associated with decreased use, as compared to publications sponsored by the MAH (p < 0.05, OR 28·2, 95% CI 4·8-166·1). CONCLUSION: Recommendations for the use of biologicals often evolve post-authorisation. MAH-sponsored studies tend to support increased use, whereas guideline recommendations, typically based on publicly sponsored studies, more often favor restriction. Rational use of biologicals requires timely evidence generation and should ideally lead to amendments in SmPC's.
Curcumin versus placebo in benign prostatic hyperplasia: a systematic review and meta-analysis.
Santana DS, Porto BC, Cardoso RB … +7 more , Lopes GMM, Gimenez LGS, Passerotti CC, Maia R, Almeida FG, da Silva Sardenberg RA, da Cruz JAS
Eur J Clin Pharmacol · 2026 Jun · PMID 42247029 · Full text
BACKGROUND: Benign prostatic hyperplasia (BPH) is a highly prevalent condition among aging men and a major cause of lower urinary tract symptoms (LUTS). Although α1-adrenoceptor blockers and 5-alpha-reductase inhibitors...
BACKGROUND: Benign prostatic hyperplasia (BPH) is a highly prevalent condition among aging men and a major cause of lower urinary tract symptoms (LUTS). Although α1-adrenoceptor blockers and 5-alpha-reductase inhibitors remain the cornerstone of treatment, their long-term use is frequently limited by adverse effects and suboptimal symptom control. Growing experimental and clinical evidence suggests that chronic prostatic inflammation plays a central role in BPH progression, raising interest in anti-inflammatory compounds such as curcumin. However, the clinical effectiveness of curcumin in BPH remains poorly defined. METHODS: We conducted a systematic review and meta-analysis of randomized and nonrandomized comparative studies evaluating curcumin versus placebo in men with BPH receiving α-blockers and/or 5-alpha-reductase inhibitors. Searches were performed in PubMed, Embase, and Cochrane CENTRAL. The primary outcome was change in International Prostate Symptom Score (IPSS). Secondary outcomes included prostate-specific antigen (PSA), prostate volume (PV), post-void residual volume (PVR), and maximum urinary flow rate (Q-max). Pooled analyses were performed using a random-effects model. RESULTS: Six studies involving 697 patients met the inclusion criteria. Compared with placebo, curcumin was associated with a significant improvement in IPSS (MD - 4.11; p = 0.0009), accompanied by reductions in PSA (MD - 0.52 ng/mL), PV (MD - 3.78 mL), and PVR (MD -2.38 mL), as well as an increase in Q-max (MD 2.09 mL/s). Subgroup analyses suggested greater symptomatic benefit among patients receiving α-blockers alone compared with those on combined α-blocker and 5-alpha-reductase inhibitor therapy. Substantial heterogeneity was observed across outcomes. CONCLUSION: Curcumin supplementation was associated with significant improvement in LUTS and functional parameters in men with BPH. Although these findings support a potential adjunctive role for curcumin, the available evidence is limited by heterogeneity and study design variability. Well-designed, large-scale randomized trials are warranted to define its clinical utility, optimal formulation, and long-term effects.
Secondary data analysis of Adverse Drug Reactions reported by healthcare professionals and patients: interventions to manage ADRs of ACE inhibitors and ARBs.
Spronk SH, Nielen JTH, Heier L … +3 more , Jessurun N, Kant A, Karapinar-Çarkit F
Eur J Clin Pharmacol · 2026 Jun · PMID 42234189 · Full text
PURPOSE: Prescribing cascades occur when an adverse drug reaction (ADR) of a first medication is treated with a second medication, potentially leading to polypharmacy and harm. While various interventions are recommended...
PURPOSE: Prescribing cascades occur when an adverse drug reaction (ADR) of a first medication is treated with a second medication, potentially leading to polypharmacy and harm. While various interventions are recommended to prevent harm, it is unknown which are implemented in daily practice. This study aims to assess the interventions implemented for ADRs of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). METHODS: This cross-sectional study analysed secondary data from spontaneous ADR reports submitted to the Netherlands Pharmacovigilance Center Lareb. Reports were included if the ADR was suspected to be caused by an ACE inhibitor or ARB and an intervention was documented. The primary outcome was the proportion of ADRs treated with (1) dose reduction, (2) discontinuation of the suspected medication, (3) discontinuation followed by medication to treat the ADR, (4) switching to alternative medication, or (5) addition of marker medication (prescribing cascade). The secondary outcome was the proportion of ADRs resolved at the time of the ADR report. RESULTS: A total of 902 ADR reports were included. The most frequent intervention was discontinuing the suspected medication, followed by introducing medication to treat the ADR (42.5%), resulting in a large proportion of resolved ADRs (46.5%). However, 11.9% of reports included prescribing cascades, resolving the ADR in only 25.2% of reports. CONCLUSION: Using real-world pharmacovigilance data, this study offers valuable insights into the treatment of ADRs of ACE inhibitors and ARBs in daily practice. Further research is needed to establish the most effective interventions for specific types of ADRs.
Population pharmacokinetics of lumefantrine in pregnant and non-pregnant Nigerian women receiving efavirenz-based antiretroviral therapy.
Akinrinade TO, Hassan IA, Adegbola AJ … +5 more , Adeleke A, Nwogu-Attah JN, Eniayewu O, Adehin A, Bolaji OO
Eur J Clin Pharmacol · 2026 Jun · PMID 42234159 · Publisher ↗
PURPOSE: Lumefantrine is a key partner drug in artemether-lumefantrine therapy, yet data describing its pharmacokinetics among women with efavirenz-based antiretroviral therapy remains limited. This study aimed to charac...
PURPOSE: Lumefantrine is a key partner drug in artemether-lumefantrine therapy, yet data describing its pharmacokinetics among women with efavirenz-based antiretroviral therapy remains limited. This study aimed to characterise the population pharmacokinetics of lumefantrine in pregnant and non-pregnant Nigerians living with HIV, evaluate the influence of pregnancy and CYP3A5 genotype, and assess the adequacy of current and alternative dosing regimens with respect to day-7 plasma concentration targets. METHODS: Plasma lumefantrine concentrations were analysed using nonlinear mixed-effects modelling in Pumas. Structural models comprising one to three compartments, along with alternative absorption models, were evaluated. Pregnancy status and CYP3A5 expressor status, among other candidate covariates, were tested using a stepwise covariate modelling procedure. Model robustness was assessed using nonparametric bootstrap resampling and simulation-based diagnostics. Monte Carlo simulations were then performed to compare the probability of achieving a day-7 lumefantrine concentration of at least 0.2 µg/mL under current versus alternative dosing regimens. RESULTS: Lumefantrine pharmacokinetics were adequately described by a two-compartment model with transit absorption. Pregnancy status and functionally relevant CYP3A5 genotype were not identified as significant covariates on lumefantrine pharmacokinetic parameters among the study population. At the currently recommended twice-daily dosing for 3 days, approximately 65% of simulated patients achieved the day-7 concentration target. Extending dosing to twice daily for 5 days increased target attainment to approximately 96%, while alternative intensified regimens also improved exposure. CONCLUSIONS: No statistically significant effect of pregnancy on lumefantrine pharmacokinetics was identified in this EFV-treated population. However, the standard 3-day dosing regimen may result in suboptimal exposure in a substantial proportion of patients. Simulation results suggest that extended dosing regimens could markedly improve day-7 target attainment, supporting further evaluation of alternative dosing strategies to optimise the efficacy of artemether-lumefantrine among people with concurrent EFV-based ART.
Influence of antihypertensive drug classes on circadian blood pressure patterns and left ventricular remodeling - a retrospective study.
Ma Q, Wang S, Chen H
Eur J Clin Pharmacol · 2026 Jun · PMID 42223692 · Publisher ↗
BACKGROUND: Circadian blood pressure (BP) abnormalities, including nondipping and reverse-dipping patterns, are increasingly recognized as major determinants of cardiovascular target-organ damage, independent of clinic B...
BACKGROUND: Circadian blood pressure (BP) abnormalities, including nondipping and reverse-dipping patterns, are increasingly recognized as major determinants of cardiovascular target-organ damage, independent of clinic BP. Antihypertensive drug classes and dosing time may differentially influence nocturnal BP control and left ventricular (LV) remodeling. However, real-world data integrating these factors remain limited, particularly in Chinesepopulations. METHODS: This retrospective, observational study included 500 adult patients with essential hypertension evaluated at a tertiary-care center between 2020 and 2024. All patients underwent valid 24-hour ambulatory BP monitoring (ABPM) and transthoracic echocardiography performed within six months of ABPM. Antihypertensive therapy was classified by drug class and dosing time (morning-only vs. evening/bedtime dosing of ≥ 1 agent). Circadian BP phenotypes were defined based on nocturnal systolic BP decline. LV mass index (LVMI) and LV geometric patterns were assessed according to standard echocardiographic criteria. Multivariable regression analyses were performed to evaluate associations between antihypertensive regimen, circadian BP indices, and LV remodeling. RESULTS: Nondipping or reverse-dipping BP patterns were present in 48.6% of patients. RAAS-blocker-based regimens and bedtime dosing were associated with significantly lower nighttime BP, greater nocturnal BP decline, reduced morning BP surge, and a higher prevalence of preserved dipping compared with non-RAAS regimens and morning-only dosing (all p < 0.01). LV hypertrophy (LVH) was observed in 27.2% of patients and was significantly more prevalent among nondippers and reverse dippers. LVMI and relative wall thickness increased progressively with worsening circadian BP phenotype (p < 0.001). In multivariable models, nondipping (OR 1.89) and reverse dipping (OR 2.64), higher nighttime systolic BP, and nocturnal hypertension were independently associated with LVH. RAAS-based therapy and bedtime dosing were associated with lower odds of LVH, with partial attenuation after adjustment for nocturnal BP indices. CONCLUSIONS: In treated hypertension, circadian BP abnormalities remain common and are strongly associated with adverse LV remodeling. Antihypertensive drug class and dosing time are important determinants of nocturnal BP control and cardiac structural changes, highlighting the clinical value of ABPM-guided, individualized treatment strategies.
Transdermal drug delivery systems in cancer therapy: advances, challenges, and future perspectives.
Arghidash F, Judaki AA, Nejad MMS … +2 more , Nazari E, Rezaei-Tavirani M
Eur J Clin Pharmacol · 2026 Jun · PMID 42219404 · Publisher ↗
Conventional cancer therapies, particularly oral and intravenous chemotherapy, are frequently associated with systemic toxicity, non-specific drug distribution, fluctuating plasma concentrations, and limited patient comp...
Conventional cancer therapies, particularly oral and intravenous chemotherapy, are frequently associated with systemic toxicity, non-specific drug distribution, fluctuating plasma concentrations, and limited patient compliance. These drawbacks have led to the development of alternative drug delivery strategies which aimed at improving therapeutic potency with minimized adverse effects. Transdermal drug delivery systems (TDDS) have emerged as a promising non-invasive technology that possesses the ability to offer sustained and controlled drug release, avoiding first-pass metabolism, and reducing systemic exposure. In the context of cancer treatment, TDDS allows for localized drug delivery and optimized pharmacokinetic control, thereby enhancing therapeutic index. Recent formulation advancements in the area of polymeric patches, microneedles, nanoliposomes, lipid and polymeric nanoparticles, nanoemulsions and physical enhancement methods such as iontophoresis and electroporation have greatly improved skin permeability and drug stability. The application of nanotechnology has also enabled the development of targeted, stimulus-responsive, and immune-modulating delivery systems. Despite the challenges posed by skin barrier function, penetration of high molecular weight drugs, interpatient variability, and translational issues, ongoing preclinical and clinical studies demonstrate the growing promise of TDDS primarily in localized and superficial malignancies, such as melanoma and non-melanoma skin cancers, with systemic applications remaining largely at the preclinical stage. This review critically evaluates the existing formulation approaches, molecular mechanisms, clinical efficacy and future prospects of TDDS in cancer treatment.
Efficacy and safety of Ongericimab in patients with hypercholesterolemia: a systematic review and meta-analysis.
Youseif AL, Younis AF, Elmezayen ZW … +8 more , Eldahrawy M, Hammad N, Hamed BM, Saleh AR, Mohamed AA, Saad OA, Ramadan AM, Awad AA
Eur J Clin Pharmacol · 2026 May · PMID 42189272 · Publisher ↗
BACKGROUND: Hypercholesterolemia represents abnormally elevated cholesterol levels and constitutes a major modifiable risk factor for cardiovascular diseases (CVDs). Low-density lipoprotein cholesterol (LDL-C) reduction...
BACKGROUND: Hypercholesterolemia represents abnormally elevated cholesterol levels and constitutes a major modifiable risk factor for cardiovascular diseases (CVDs). Low-density lipoprotein cholesterol (LDL-C) reduction remains the primary therapeutic target. However, many high-risk patients fail to achieve recommended LDL-C targets with conventional lipid-lowering therapies. Ongericimab is a new humanized recombinant monoclonal antibody targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). We aimed to evaluate the efficacy and safety of Ongericimab compared to placebo in patients with hypercholesterolemia. METHODS: Following PRISMA guidelines, we searched PubMed, Scopus, Cochrane Library, Web of Science and Google Scholar through February 2025 for randomized controlled trials (RCTs) comparing Ongericimab versus placebo. Outcomes were pooled as mean difference (MD) or odds ratio (OR) with 95% confidence intervals (CIs) using random-effects models. RESULTS: Five RCTs comprising 1421 patients were included. Ongericimab significantly reduced LDL-C across all dosing regimens: 150 mg every 2 weeks (MD -69.48%, 95% CI: -73.02 to -65.94), 300 mg every 4 weeks (MD -61.82%, 95% CI: -66.66 to -56.98), and 450 mg every 4 weeks (MD -73.11%, 95% CI: -89.56 to -56.65); all p < 0.00001. Significant reductions were also observed in lipoprotein(a) (MD range: -44.81% to -50.06%), apolipoprotein B, non-HDL cholesterol, triglycerides, and total cholesterol, along with significant increases in HDL cholesterol and apolipoprotein A1. Adverse event rates were comparable between groups, with a pooled reduction OR of 0.85 (95% CI: 0.73-0.99) for overall treatment-emergent adverse events, favoring Ongericimab. CONCLUSION: This meta-analysis demonstrates that Ongericimab is effective and safe for improving lipid parameters in patients with hypercholesterolemia and dyslipidemia. These findings support Ongericimab as a valuable therapeutic option for patients requiring additional LDL-C reduction beyond conventional therapy. Further long-term studies are recommended to confirm cardiovascular outcomes.
Safety and efficacy of intravenous tenecteplase in patients with acute ischemic stroke in the extended time window: an updated meta-analysis.
Rejili M, Khan Y, Rawat A … +5 more , Haouala F, Hasanli L, Shaheen A, Hagag AM, Alimova Z
Eur J Clin Pharmacol · 2026 May · PMID 42189257 · Publisher ↗
BACKGROUND: We performed an updated systematic review and meta-analysis to evaluate tenecteplase 0.25 mg/kg in the extended time window. METHODS: MEDLINE was searched via PubMed, Scopus, and Web of Science from inception...
BACKGROUND: We performed an updated systematic review and meta-analysis to evaluate tenecteplase 0.25 mg/kg in the extended time window. METHODS: MEDLINE was searched via PubMed, Scopus, and Web of Science from inception to February 2026, with trial registries also screened. Eligible trials were RCTs of adults treated beyond 4.5 h from last known well or with wake-up stroke, comparing IV tenecteplase 0.25 mg/kg with placebo or standard care. Primary efficacy outcomes were 90-day mRS 0-1 and mRS 0-2, and primary safety outcomes were symptomatic intracranial hemorrhage and death. RoB 2 and GRADE were used to assess risk of bias and certainty. Risk ratios were pooled using a random effects model. RESULTS: Nine RCTs, including 4,000 participants, met eligibility criteria. Tenecteplase was associated with a modest increase in excellent functional outcome (9 studies, 4000 patients, RR 1.12, 95% CI 1.027 to 1.22, p = 0.01, I: 14.9%) and favorable functional outcome (9 studies, 4000 patients, RR 1.06, 95% CI 1.01 to 1.11, p = 0.0091, I: 10.6%). Tenecteplase showed a significantly higher risk of sICH (9 studies, 4000 patients, RR 1.86, 95% CI 1.065 to 3.24, p = 0.029, I: 21.8%), while no difference was found in death (9 studies, 4000 patients, RR 1.006, 95% CI 0.85 to 1.19, p = 0.95, I: 35.5%). GRADE certainty was high for favorable outcome and death, and moderate for excellent outcome, sICH, reperfusion, and parenchymal hematoma type 2. CONCLUSIONS: In extended window acute ischemic stroke, tenecteplase 0.25 mg/kg improved 90-day functional outcomes and increased reperfusion, but it increased intracranial hemorrhage, including sICH. These findings support careful use in imaging selected patients, with attention to bleeding risk.
"Ondansetron augmentation for obsessive-compulsive disorder: A systematic review and meta-analysis of randomized placebo-controlled trials".
Mohammad A, Ibrahim M, Khan AM … +4 more , Pervaiz U, Aijaz S, Nasrullah MH, Jamil H
Eur J Clin Pharmacol · 2026 May · PMID 42178423 · Publisher ↗
BACKGROUND: A substantial proportion of adults with obsessive-compulsive disorder (OCD) experience persistent symptoms despite optimized first-line treatment with exposure and response prevention and/or serotonin reuptak...
BACKGROUND: A substantial proportion of adults with obsessive-compulsive disorder (OCD) experience persistent symptoms despite optimized first-line treatment with exposure and response prevention and/or serotonin reuptake inhibitors (SRIs). Ondansetron, a selective 5-hydroxytryptamine-3 (5-HT3) receptor antagonist with plausible circuit-level relevance to cortico-striato-thalamo-cortical dysfunction, has been evaluated as an augmentation strategy. Still, evidence is dispersed across small randomized trials. METHODS: We conducted a PRISMA 2020-adherent systematic review and random-effects meta-analysis (PROSPERO: CRD420261302132). Embase (Ovid and Embase.com), MEDLINE, PubMed, and Scopus were searched from inception to 12 February 2026. Eligible studies were randomized, double-blind, placebo-controlled trials of oral ondansetron augmentation in adults (≥ 18 years) with OCD on stable background treatment. The primary outcome was change in Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) total score, pooled at prespecified acute windows (week 4, ~week 8 primary, week 12). Secondary outcomes included Y-BOCS obsession and compulsion subscales. Risk of bias was assessed using RoB 2. Random-effects models (DerSimonian-Laird) were used; Wan's method was applied when required. RESULTS: Five trials (total N = 289) were included. Ondansetron augmentation was associated with greater improvement in Y-BOCS total score versus placebo at week 4 (MD 2.63; 95% CI 0.87-4.39; I²=62%); heterogeneity resolved after excluding one influential study (MD 1.94; 0.37-3.51; I²=0%). At week 8 (four trials; N = 244), benefit was larger (MD 5.53; 3.45-7.60; I²=48%) and remained robust in sensitivity analysis (MD 6.76; 5.81-7.71; I²=0%). At week 12 (three trials; N = 200), effects persisted (MD 6.41; 4.28-8.53; I²=55%) with reduced heterogeneity after excluding one study (MD 5.06; 2.82-7.30; I²=0%). In two trials reporting subscales (N = 214), obsessions improved at weeks 4 and 8 (overall MD 2.67; 1.66-3.67; I²=0%), while compulsions showed a smaller, later signal (overall MD 1.02; 0.19-1.86; I²=0%). Safety reporting was variably detailed across trials; known QT-prolongation considerations remain relevant for off-label use. CONCLUSIONS: In randomized, placebo-controlled trials, ondansetron augmentation was associated with greater improvement in clinician-rated OCD severity than placebo over short-term follow-up, with signals emerging by week 4 and persisting through 8-12 weeks. However, these findings should be interpreted cautiously because the evidence base is small, geographically concentrated, and partly influenced by individual studies. The current evidence should therefore be considered preliminary and hypothesis-generating rather than definitive. Larger multicenter trials with standardized background SRI optimization, preregistered outcomes, and rigorous safety monitoring are required before routine clinical adoption can be considered.
Development and validation of high-dose methotrexate population pharmacokinetic models to inform clinical decisions on dosing.
Blackman MH, Yelvington B, Beck C … +2 more , Cortez M, Choi L
Eur J Clin Pharmacol · 2026 May · PMID 42174327 · Full text
PURPOSE: High-dose methotrexate is an effective treatment for adult and pediatric patients with acute lymphoblastic leukemia, osteosarcoma, and lymphoma. However, its clearance is highly variable, and delayed clearance c...
PURPOSE: High-dose methotrexate is an effective treatment for adult and pediatric patients with acute lymphoblastic leukemia, osteosarcoma, and lymphoma. However, its clearance is highly variable, and delayed clearance can lead to significant toxicity. This study aimed to identify a population pharmacokinetic model that accurately characterizes high-dose methotrexate clearance in an adult population. METHODS: We developed a new population pharmacokinetic model using a training dataset derived from a cohort of 208 adult patients who received high-dose methotrexate at Vanderbilt University Medical Center. To assess predictive performance, we evaluated both our model and several externally developed models using an independent test dataset. RESULTS: The final model was a three-compartment model incorporating body surface area as a covariate on all pharmacokinetic parameters, and serum creatinine and sex as covariates on clearance. Our newly developed model predicted with the most accuracy and precision at the first concentration measurement, taken at 24 h. Our model, along with five external models, was selected based on predictive performance for further assessment with maximum a posteriori Bayesian forecasting to compare predictions at the individual-level. The model by Hui et al. was more accurate at 48 h, while our model performed similarly at 72 h. CONCLUSION: These findings suggest an optimal strategy for therapeutic drug monitoring and dosing decisions: use our model for prediction at the 24 h mark when no prior drug levels are available, followed by Bayesian forecasting using our new model supplemented by the Taylor model.
Dysesthesia associated with GLP-1 agonist therapies: data-mining analysis and literature review.
Laroche ML, Géniaux H, Jardou M
Eur J Clin Pharmacol · 2026 May · PMID 42168638 · Full text
PURPOSE: An increasing number of anecdotal reports on social media platforms and medical blogs describe dysesthesia, particularly burning skin sensations, in association with glucagon-like peptide-1 receptor (GLP-1R) ago...
PURPOSE: An increasing number of anecdotal reports on social media platforms and medical blogs describe dysesthesia, particularly burning skin sensations, in association with glucagon-like peptide-1 receptor (GLP-1R) agonists. We performed a pharmacovigilance data-mining analysis to characterise cases of dysesthesia related to GLP-1R. METHODS: We conducted a disproportionality analysis using VigiBase data on GLP-1R (Anatomical Therapeutic Chemical classification: ATC code A10BJ) and tirzepatide, focusing on the HLT (High Level Term) "Paraesthesia and dysesthesia", with the Information Component (IC). Additionally, we reviewed all narratives of dysesthesia cases in the French Pharmacovigilance database to extract clinical and pharmacological characteristics. A literature review complemented this analysis. RESULTS: Exenatide was significantly associated with hypoesthesia or oral paraesthesia, semaglutide and tirzepatide with hyperaesthesia, and semaglutide with dysesthesia and burning sensation. Dysesthesia appears to be dose-dependent, occurring more frequently at higher doses and with more potent GLP-1R, whether used for weight management or type 2 diabetes. Discontinuation was often performed, followed by spontaneous favourable outcomes, and cases of rechallenge were observed. Skin burning sensations represent a distinctive form of dysesthesia. CONCLUSION: Pharmacovigilance quantitative and qualitative data strengthens evidence for dysesthesias associated with GLP-1R agonists already observed in clinical trials of semaglutide, tirzepatide, and retatrutide.
The influence of hydroxychloroquine on the risk of pre-eclampsia, hypertension, and premature delivery in patients with systemic lupus erythematosus during pregnancy: a meta-analysis.
Liu D, Chen Y, Liu F
Eur J Clin Pharmacol · 2026 May · PMID 42168466 · Publisher ↗
OBJECTIVE: To evaluate the associations between hydroxychloroquine (HCQ) use and the risks of pre-eclampsia, hypertensive disorders of pregnancy (HDP), and preterm delivery in pregnant women with systemic lupus erythemat...
OBJECTIVE: To evaluate the associations between hydroxychloroquine (HCQ) use and the risks of pre-eclampsia, hypertensive disorders of pregnancy (HDP), and preterm delivery in pregnant women with systemic lupus erythematosus (SLE). METHODS: PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science were systematically searched from inception to May 30, 2024, for randomized controlled trials or observational studies investigating HCQ use in pregnant women with SLE. Study quality was assessed using the Newcastle-Ottawa Scale, and meta-analyses were performed using RevMan 5.1 software. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models as appropriate. RESULTS: Nine studies were included in the meta-analysis. Compared with no HCQ use, HCQ use was not associated with statistically significant differences in the incidence of pre-eclampsia (4 studies, 1145 patients, OR = 1.11, 95% CI 0.60-2.06, P > 0.05), miscarriage (3 studies, 395 patients, OR = 1.27, 95% CI 0.72-2.25, P > 0.05), HDP (4 studies, 4787 patients, OR = 0.70, 95% CI 0.09-5.65, P > 0.05), or preterm delivery (9 studies, 2503 patients, OR = 0.78, 95% CI 0.44-1.39, P > 0.05). However, HCQ use was associated with a significantly lower risk of fetal growth restriction (FGR) (3 studies, 278 patients, OR = 0.41, 95% CI 0.18-0.93, P < 0.05) and gestational diabetes mellitus (GDM) (2 studies, 563 patients, OR = 0.28, 95% CI 0.17-0.48, P < 0.05). CONCLUSIONS: This meta-analysis demonstrated that hydroxychloroquine administration during pregnancy could not reduce the incidence of gestational complications. The results are inconsistent with those of previous primary studies, which may be attributed to the absence of parity-based stratification in the original studies. Accordingly, close attention should be paid to the adverse reactions of hydroxychloroquine, which should be used carefully. Further high-quality studies with subgroup analysis based on parity are strongly recommended in the future.
Response to comment on "CYP2C19 genotyping and mavacamten: predicting outcomes in normal, intermediate and rapid metabolisers in obstructive hypertrophic cardiomyopathy".
Kasolo Y, Cooper RM
Eur J Clin Pharmacol · 2026 May · PMID 42133050 · Publisher ↗
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