European Journal Of Clinical Pharmacology[JOURNAL]
Sun
200 papers
Efficacy and safety of Ensitrelvir in COVID-19 patients: a systematic review and meta-analysis with focus on viral clearance and RNA change.
Nofal S, Al-Said O, Alnimer K … +4 more , Sarah JM, Alam TA, Ali O, Abuquteish D
Eur J Clin Pharmacol · 2026 Jun · PMID 42371105 · Publisher ↗
BACKGROUND: Coronavirus Disease (COVID-19), which is caused by SARS-CoV-2 virus, led to a worldwide pandemic in late 2019, thus challenged the healthcare infrastructure across the world, creating an urgent need for the d...
BACKGROUND: Coronavirus Disease (COVID-19), which is caused by SARS-CoV-2 virus, led to a worldwide pandemic in late 2019, thus challenged the healthcare infrastructure across the world, creating an urgent need for the development of effective antiviral medications to handle its spread and evolving strains. OBJECTIVE: This Meta-Analysis aims to investigate the overall efficacy and safety of Ensitrelvir. METHODS: We conducted a systematic review and meta-analysis, according to PRISMA guidelines, searching web databases for relevant literature. We limited our eligibility to randomized clinical trials involving mild-to-moderate COVID-19 patients. RESULTS: Our study included four randomized controlled trials involving a total of 2,890 patients. For patients with mild-to-moderate Covid-19, treatment with Ensitrelvir (125 mg or 250 mg) was associated with significantly improved outcomes compared to placebo across several metrics: higher viral clearance was observed for 125 mg [MD = - 37.74, P < 0.00001] and 250 mg [MD = - 35.02, P < 0.00001]; greater reductions in viral RNA were achieved by 125 mg [MD = -1.41, P < 0.00001] and 250 mg [MD = -1.37, P < 0.00001]; and a significantly lower proportion of patients maintained a positive viral titer at 125 mg [RR 0.08, P < 0.00001, I = 82%] and 250 mg [RR 0.10, P < 0.00001, I = 16%]. Ultimately, there were no significant differences in reported outcomes between the 125 mg and 250 mg Ensitrelvir dosage groups. CONCLUSION: This systematic review and meta-analysis support Ensitrelvir efficacy and safety in promoting rapid viral clearance and greater reduction in viral RNA in mild-to-moderate or asymptomatic COVID-19 patients, justifying its integration into outpatient treatment protocols while emphasizing the need for further large-scale, variant-inclusive studies to validate and extend these findings. REGISTRATION: PROSPERO (CRD420251030953).
Comparing National Health Technology Assessment approaches and the new European Joint Clinical Assessment framework: The case of onco-hematological medicines.
Starinieri B, Allocati E, Gerardi C … +2 more , Joppi R, Banzi R
Eur J Clin Pharmacol · 2026 Jun · PMID 42371064 · Publisher ↗
PURPOSE: To analyze national-level evaluations conducted by selected Health Technology Assessment (HTA) bodies and compare them with the methodological framework outlined in the European HTA Regulation for Joint Clinical...
PURPOSE: To analyze national-level evaluations conducted by selected Health Technology Assessment (HTA) bodies and compare them with the methodological framework outlined in the European HTA Regulation for Joint Clinical Assessment (JCA), in order to assess whether JCA would improve alignment among national practices. METHODS: We used onco-hematological medicines as a case model. From the European Medicine Agency (EMA) website, we identified onco-hematological medicines licensed from January 2023 to April 2025 and the pivotal trials supporting their marketing authorization (MA). We retrieved the reports of seven national HTA agencies and examined the rationale and evidence underlying the agencies' evaluation and their final recommendations. To estimate how the JCA opinion would have changed compared to those taken by the national HTA authorities, we developed a set of possible Population, Intervention, Comparators, and Outcomes (PICOs) and applied JCA criteria to selected medicines. RESULTS: We assessed ten trials supporting the MA of eight medicines. All except momelotinib were approved based on one single pivotal trial. Six were single-arm studies. By June 2025, 22 national HTA reports were available for six medicines, incorporating pivotal trial data and indirect treatment comparisons for five medicines. Overall, recommendations from HTA agencies varied. The PICO scoping process generated at least four PICOs per medicine, reflecting high heterogeneity across countries. The limited evidence at the time of MA was insufficient to address all the PICOs. CONCLUSION: Although JCA strengthens procedural harmonization, the current HTA fragmentation may persist due to the proliferation of PICOs and divergent interpretations of evidence.
The efficacy of letrozole in the medical management of ectopic pregnancy: a systematic review and meta-analysis.
Abdel-Qader DH, Abdelsattar NK, Albassam A … +6 more , Al-Kubais KA, Taybeh E, Al Mazrouei N, Ibrahim R, Ibrahim OM, Taha TAA
Eur J Clin Pharmacol · 2026 Jun · PMID 42362983 · Publisher ↗
OBJECTIVE: This review aimed to assess the efficacy and safety of letrozole, administered either as monotherapy or combined with methotrexate, for the treatment of ectopic pregnancy (EP). METHODS: Following established g...
OBJECTIVE: This review aimed to assess the efficacy and safety of letrozole, administered either as monotherapy or combined with methotrexate, for the treatment of ectopic pregnancy (EP). METHODS: Following established guidelines (PRISMA), a systematic review and meta-analysis was conducted. Major online research databases (Web of Science, PubMed, Scopus, and Cochrane Library) were searched for studies comparing letrozole to methotrexate in women diagnosed with EP via ultrasound, from the earliest available records up to November 5, 2024. The combined results were analyzed using risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). The quality of the included studies was evaluated using ROB-2 and ROBINS-I tools. RESULTS: Eight studies (five randomized and three non-randomized trials) involving 548 participants were included. Letrozole monotherapy achieved a higher treatment success rate compared to methotrexate (6 studies, 376 patients, RR 1.10, 95% CI [1.01, 1.20], p = 0.03). Combining letrozole with methotrexate showed comparable success rates to methotrexate alone (2 studies, 161 patients, RR 1.09, 95% CI [0.96, 1.23], p = 0.17). On day 4, β-human chorionic gonadotropin (β-hCG) levels decreased faster in both the letrozole monotherapy (5 studies, 291 patients, MD -131.15 mIU/mL, 95% CI [-220.77, -41.52], p = 0.004) and combination groups (2 studies, 136 patients, MD -188.79 mIU/mL, 95% CI [-242.07, -135.52], p < 0.00001). Letrozole monotherapy resulted in a smaller reduction in platelet count (2 studies, 76 patients, MD 81.61 × 10³/µL, 95% CI [40.11, 123.10], p = 0.0001) and better-preserved liver enzymes, such as ALT (3 studies, 76 patients, MD -21.27 IU/L, 95% CI [-24.42, -18.12], p < 0.00001). No differences were noted in anti-Müllerian hormone (AMH) levels (2 studies, 39 patients, MD -0.01 ng/mL, 95% CI [-0.40, 0.38], p = 0.97). CONCLUSIONS: Letrozole, especially when used as the only treatment, may be a more effective and potentially safer alternative to methotrexate for medically treating EP. However, larger, higher-quality research studies are necessary to confirm these findings and to determine the best way to use letrozole.
Detection of intravenous drug physicochemical incompatibilities in clinical practice: e-Harvis compared to reference tools.
Ammor W, Moynard J, Lindenberg F … +1 more , Navas D
Eur J Clin Pharmacol · 2026 Jun · PMID 42362916 · Publisher ↗
INTRODUCTION: Physicochemical incompatibilities (PCIs) resulting from the simultaneous intravenous administration of drugs through Y-sites represent a potential source of iatrogenic adverse events in hospital settings, p...
INTRODUCTION: Physicochemical incompatibilities (PCIs) resulting from the simultaneous intravenous administration of drugs through Y-sites represent a potential source of iatrogenic adverse events in hospital settings, particularly in situations involving polymedication and limited venous access. Although several compatibility databases are available, their coverage remains incomplete and their recommendations may be inconsistent. MATERIALS AND METHODS: A prospective observational study was conducted over 30 half-day periods in four hospital departments (conventional haematology, protected haematology, adult intensive care and resuscitation (ICR) and paediatric oncology) to identify drug pairs co-administered through Y-sites and assess their compatibility using five reference tools (Handbook on Injectable Drugs, Table of Y-Site Compatibility of Injectable Drugs from the University Hospitals of Geneva, King Guide to Parenteral Admixtures, Micromedex, and Stabilis). An overall compatibility response (compatible, incompatible or unknown) was defined as the classification derived from these five tools, with incompatible assigned in case of equal classifications. This overall response was used as a comparator to evaluate the performance of e-Harvis, a decision-support tool combining bibliographic compatibility data with a predictive model used when experimental evidence is unavailable. RESULTS: A total of 765 administered pairs were identified, of which 56.1% were drug/drug pairs. Only one visible PCI was observed during the observation period. According to the overall response, 60.3% of pairs were compatible, 11.4% were incompatible and 28.4% were unknown. E-Harvis concluded that 32.8% were compatible, 10.6% were incompatible and 56.6% were unknown, with a 55.8% concordance with the overall response. CONCLUSIONS: The tool also provided faster access to compatibility information and broader standalone coverage than individual reference databases for drug-drug pairs. In the absence of a validated gold standard for intravenous compatibility assessment, these findings suggest that e-Harvis may constitute a useful complementary decision-support tool for synthesising heterogeneous evidence and facilitating compatibility assessment in complex infusion settings.
Efficacy and safety of doravirine/islatravir for the treatment of HIV-1: a systematic review and meta-analysis of randomized controlled trials with GRADE assessment.
Abdeldayem MR, Elsherbeeny A, Beddor A
Eur J Clin Pharmacol · 2026 Jun · PMID 42343061 · Publisher ↗
PURPOSE: Two-drug antiretroviral regimens are being investigated as alternatives to standard three-drug therapy for HIV-1. Doravirine/islatravir is a once-daily oral combination with promising efficacy and safety, but it...
PURPOSE: Two-drug antiretroviral regimens are being investigated as alternatives to standard three-drug therapy for HIV-1. Doravirine/islatravir is a once-daily oral combination with promising efficacy and safety, but its overall clinical performance has not been systematically quantified. This study evaluated the efficacy and safety of doravirine/islatravir compared with standard triple option therapy in adults living with HIV-1. METHODS: PubMed, Scopus, Web of Science, and the Cochrane Library were systematically searched for phase III randomized controlled trials comparing doravirine/islatravir with standard triple option therapy. Eligible studies were independently screened, and data were extracted and pooled using R software. RESULTS: Six phase III trials involving 3,518 adults were included. At 48 weeks, doravirine/islatravir was associated with a significantly lower risk of virological failure (HIV-1 RNA ≥ 50 copies/mL) compared with standard triple option therapy (RR: 0.51, 95% CI [0.30-0.88]; P = 0.015). Rates of virological suppression (< 50 and < 200 copies/mL) were comparable between groups. No significant differences were observed in overall, serious, or grade 3-4 adverse events, or treatment discontinuation due to adverse events. Dose-stratified analyses showed that the 100/0.75 mg formulation was associated with significant declines in CD4 cell count and total lymphocyte count at 48 weeks, whereas the optimized 100/0.25 mg dose showed no significant immunological differences compared with standard triple option therapy. CONCLUSIONS: Doravirine/islatravir is an effective and generally well-tolerated two-drug regimen for HIV-1. The optimized 100/0.25 mg formulation maintained virological efficacy without significant short-term immunological differences versus standard triple option therapy; however, longer follow-up is needed to confirm its long-term immunological safety.
Critical analysis of digitalis glycosides: declining use but increasing poison-center exposure cases for digitoxin.
Ecker PAM, Schaper A, Bräunig HJ … +1 more , Seifert R
Eur J Clin Pharmacol · 2026 Jun · PMID 42334625 · Full text
PURPOSE & BACKGROUND: Belonging to one of the oldest drug classes in cardiovascular-medicine, the scientific interest in NaK-ATPase inhibitors (NKA-inhibitors, digitalis glycosides) has increased once again after the pub...
PURPOSE & BACKGROUND: Belonging to one of the oldest drug classes in cardiovascular-medicine, the scientific interest in NaK-ATPase inhibitors (NKA-inhibitors, digitalis glycosides) has increased once again after the publication of the recent DIGIT-HF study. This analysis and scoping review aim to assess long-term prescribing trends of NKA-inhibitors and poison center data to investigate the discrepancy between declining use and increasing poison center reports involving digitoxin in Germany. METHODS: By using prescription data (defined daily dose, DDD) and poison center records between 1990 and 2023 in Germany we conducted a pharmacological, pharmacoeconomic and toxicological analysis of the four NKA-inhibitors digitoxin, digoxin, acetyldigoxin and metildigoxin. For identifying trend changes and prescribing trends, we used joinpoint regression and DDD-half-time analyses. RESULTS: The DDD of NKA-inhibitors declined substantially over our investigated timeframe. Reported exposure cases involving digitoxin, recorded by the GIZ-Nord poison center, showed a significant and continuous increase. Population-adjusted exposure cases increased by 4.65% per year. Exposure-adjusted exposure cases per 1 mio. DDD increased by 11.80% per year. The data for reported cases involving digoxin showed large year-to-year variability and no significant increase in reported case numbers. The PRISM DDD-half-time analysis showed big differences between the four substances, with digitoxin exhibiting the longest DDD-half-time despite the absence of supportive evidence in the form of clinical trials, suggesting a dissociation between evidence and real-world prescriptions. CONCLUSIONS: Prescription volumes decrease but digitoxin is associated with steadily increasing reports of exposure cases from poison center data. This indicates discrepancies between prescribing trends and real-world exposure patterns and highlights the importance for patient selection and careful monitoring, especially in elderly patients.
Interpreting neutral findings in CA-AKI prevention trials: additional methodological considerations.
Bibi Z, Ali K
Eur J Clin Pharmacol · 2026 Jun · PMID 42334472 · Publisher ↗
Abstract loading — click title to view on PubMed.
The effect of Pemafibrate on glucose metabolism and FGF21: a systematic review and meta-analysisa of randomized controlled trials.
Li H, Yu H, Sohouli MH
Eur J Clin Pharmacol · 2026 Jun · PMID 42329272 · Publisher ↗
BACKGROUND: Pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) modulator, has shown potential in improving metabolic parameters. However, its effects on key metabolic biomarkers and fibrobl...
BACKGROUND: Pemafibrate, a selective peroxisome proliferator-activated receptor alpha (PPARα) modulator, has shown potential in improving metabolic parameters. However, its effects on key metabolic biomarkers and fibroblast growth factor 21 (FGF21), have not been fully elucidated. To evaluate the effects of Pemafibrate on fasting blood glucose (FBG), insulin, HbA1c, HOMA-IR, and FGF21 through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, SCOPUS, and Embase databases from their inception until November 2025. RCTs assessing the effects of Pemafibrate on the selected metabolic biomarkers were included and the weighted mean differences (WMD) for each outcome were calculated using a random-effects model. RESULTS: A total of 14 RCTs with 4084 participants were included in the present meta-analysis. Pemafibrate significantly reduced FBG (11 studies, 3273 patients, WMD = -0.47 mmol/L, 95% CI: -0.70 to -0.24), insulin levels (7 studies, 2102 patients, WMD = -30.72 pmol/L, 95% CI: -42.08 to -19.36), and HOMA-IR (8 studies, 2381 patients, WMD = -1.60, 95% CI: -2.27 to -0.93). Additionally, FGF21 levels were significantly increased (7 studies, 2178 patients, WMD = 3.30 pg/mL, 95% CI: 2.57 to 4.04). The effect on HbA1c was marginally non-significant (10 studies, 3065 patients, WMD = 0.02%, 95% CI: 0.00 to 0.05). Subgroup analysis revealed that lower duration of Pemafibrate intake were associated with significant improvements in FBG, while higher doses (> 0.2 mg/day) had more pronounced effects on FGF21 and glucoe metabolism. Meta-regression indicated that treatment duration was positively correlated with reductions in insulin levels. The overall GRADE quality assessment was rated as very good, supporting a moderate-to-high level of confidence. CONCLUSIONS: Pemafibrate significantly improves glucose metabolism, insulin sensitivity, and increases FGF21 levels, making it a promising therapeutic option for patients with metabolic disorders.
A decade of progress in small-cell lung cancer (2015-2025): a narrative review.
Petrelli F, Dottorini L, Ghidini A … +1 more , Iaculli A
Eur J Clin Pharmacol · 2026 Jun · PMID 42324360 · Publisher ↗
INTRODUCTION: Small-cell lung cancer (SCLC) accounts for 13-15% of lung-cancer diagnoses but nearly one quarter of lung-cancer-related deaths. Until 2015, the combination of platinum-etoposide chemotherapy, thoracic radi...
INTRODUCTION: Small-cell lung cancer (SCLC) accounts for 13-15% of lung-cancer diagnoses but nearly one quarter of lung-cancer-related deaths. Until 2015, the combination of platinum-etoposide chemotherapy, thoracic radiotherapy and prophylactic cranial irradiation (PCI) had kept median overall survival broadly stable at ≈ 12 months in extensive-stage (ES-SCLC) and ≈ 24 months in limited-stage (LS-SCLC) disease. We summarise the key therapeutic advances of the last decade. MATERIALS AND METHODS: This is a curated narrative review. PubMed/MEDLINE, Embase, ClinicalTrials.gov, FDA and EMA releases and ASCO/ESMO/WCLC abstracts published between January 2015 and May 2025 were searched for phase II/III trials, regulatory approvals and biomarker studies in SCLC. Quantitative pooling was not performed. Practice-changing trials, selected pivotal phase II studies that led to regulatory approval, translational papers that re-defined the molecular taxonomy and informative negative trials were prioritised for in-depth discussion. A PRISMA-style flow diagram (Fig. 1) summarises the selection process. RESULTS: Consolidative thoracic radiotherapy improved 2-year OS in ES-SCLC responders (CREST: 13% vs. 3%; HR 0.84, 95% CI 0.69-1.01) and brain-MRI surveillance preserved cognition while replacing routine PCI in patients with ES-SCLC who had access to neuro-imaging. IMpower133 and CASPIAN established first-line chemo-immunotherapy: adding atezolizumab or durvalumab to platinum-etoposide extended median OS by ≈ 2-3 months (IMpower133: 12.3 vs. 10.3 months, HR 0.70, 95% CI 0.54-0.91; CASPIAN: 13.0 vs. 10.3 months, HR 0.73, 95% CI 0.59-0.91) and approximately doubled 18-month survival; 5-year OS now reaches 12-13%. Lurbinectedin produced a 35% response rate in platinum-sensitive relapse in a single-arm phase II study; the confirmatory phase III ATLANTIS trial was negative. Trilaciclib reduced severe chemotherapy-induced myelosuppression. Molecular profiling re-segregated SCLC into ASCL1- (SCLC-A), NEUROD1- (SCLC-N), POU2F3- (SCLC-P) and YAP1/inflamed-defined (SCLC-I) subtypes, supporting the development of subtype-directed trials. DLL3 has re-emerged as a target via the bispecific engager tarlatamab (DeLLphi-301: ORR 40%, mDOR 12 months) and next-generation antibody-drug conjugates. In LS-SCLC, durvalumab consolidation up to 24 months after chemoradiotherapy improved median OS from 33.4 to 55.9 months (ADRIATIC; HR 0.73, 95% CI 0.57-0.93). Maintenance lurbinectedin plus atezolizumab more than doubled median PFS after induction chemo-immunotherapy in IMforte (5.4 vs. 2.1 months; HR 0.54, 95% CI 0.43-0.67) and improved median OS (13.2 vs. 10.6 months; HR 0.73, 95% CI 0.57-0.95). Several phase III trials in this period were negative (KEYNOTE-604, CheckMate-451, CheckMate-331, SKYSCRAPER-02, ATLANTIS, TAHOE, MERU). CONCLUSIONS: SCLC therapy has shifted from uniform cytotoxic treatment to a tiered, mechanism-driven algorithm that incorporates PD-L1 blockade, targeted cytotoxics, myeloprotection and refined radiotherapy, raising long-term survival above 20% in selected populations. From a European-practice perspective, current best practice is platinum-etoposide plus a PD-L1 inhibitor for treatment-naïve ES-SCLC, thoracic consolidation radiotherapy in selected responders, lurbinectedin or DLL3-directed clinical trials at relapse, and durvalumab consolidation after chemoradiation in LS-SCLC. Outstanding challenges include a low absolute survival gain from chemo-IO, the absence of validated predictive biomarkers, lineage plasticity, and unequal global access to new agents.
Evidence on medicines use and safety during pregnancy: pharmacovigilance or pharmacodrowsinesss ?
Braillon A
Eur J Clin Pharmacol · 2026 Jun · PMID 42321458 · Publisher ↗
Abstract loading — click title to view on PubMed.
Correspondence: Strengthening evidence traceability in written drug promotion to support rational prescribing.
Vijayasimha M, Srikanth M
Eur J Clin Pharmacol · 2026 Jun · PMID 42321438 · Publisher ↗
Written promotional materials from pharmaceutical companies continue to influence prescribing behaviour despite evolving regulatory oversight. Recent evidence from the European Journal of Clinical Pharmacology highlights...
Written promotional materials from pharmaceutical companies continue to influence prescribing behaviour despite evolving regulatory oversight. Recent evidence from the European Journal of Clinical Pharmacology highlights persistent structural limitations in how promotional claims are framed and governed. This correspondence critically examines these findings within the context of contemporary clinical pharmacology, global prescribing pressures, and emerging digital promotion ecosystems. We identify a governance gap between content compliance and evidentiary accountability, and propose an Evidence-Linked Promotion Dossier framework to improve transparency, traceability, and currency of promotional claims. Strengthening evidence linkage in promotion has the potential to support rational prescribing, reduce low-value drug use, and enhance global medicines governance.
Efficacy of different pharmacological therapies for diffuse cutaneous systemic sclerosis: a systematic review and network meta-analysis.
Chen X, Yuan F, Wang K … +1 more , Yin J
Eur J Clin Pharmacol · 2026 Jun · PMID 42319483 · Publisher ↗
OBJECTIVE: This study aims to compare the effectiveness of different pharmacological therapies for diffuse cutaneous systemic sclerosis (dcSSc) through a network meta-analysis (NMA). METHODS: Randomized controlled trials...
OBJECTIVE: This study aims to compare the effectiveness of different pharmacological therapies for diffuse cutaneous systemic sclerosis (dcSSc) through a network meta-analysis (NMA). METHODS: Randomized controlled trials (RCTs) on pharmacological interventions for dcSSc were systematically searched in PubMed, Embase, Cochrane Library, and Web of Science up to 2026. A Bayesian network meta-analysis was carried out using Markov Chain Monte Carlo (MCMC) methods via R software and its GeMtc package. Outcomes assessed included Modified Rodnan Skin Score (MRSS), pulmonary functions (forced vital capacity [FVC], and diffusing capacity of the lung for carbon monoxide [DLCO]), and Health Assessment Questionnaire (HAQ). Effect sizes were reported as standardized mean differences (SMDs) with corresponding 95% credible intervals (95% CrIs). RESULTS: A total of 20 RCTs involving 1,760 patients and 16 interventions were included. The results revealed that rituximab was the most effective intervention for reducing MRSS (SMD = - 3.4, 95% CrI (- 4.2, - 2.7)), followed by cyclophosphamide (CTX) (SMD = - 2.8, (- 3.3, - 2.2)), and belimumab (SMD = - 1.5, (- 2.5, - 0.39)). Belimumab (SMD = 1.9, (0.75, 3.1)) and CTX (SMD = 1.3, (0.86, 1.8)) topped FVC improvement. Methotrexate (MTX) was the most effective for enhancing DLCO (SMD = 0.52, (0.046, 0.99)). Belimumab (HAQ: SMD = - 3.8, (- 5.5, - 2.1)) and CTX (HAQ: SMD = - 2.9, (- 3.4, - 2.3)) were significantly effective in lowering HAQ scores. CONCLUSION: B-cell-targeted therapies (e.g., rituximab and belimumab) seemed to outperform other therapeutic agents in lowering MRSS and HAQ scores. Conventional immunosuppressants (e.g., CTX and MTX) might be more effective in enhancing pulmonary functions. Treatment strategies should be tailored according to the extent and severity of organ involvement.
Candidate-gene-based study of CYP3A-related single-nucleotide polymorphisms using 4β-hydroxycholesterol/cholesterol ratio as biomarker in a Japanese cohort.
Tanaka R, Suzuki Y, Koyama T … +12 more , Sumimoto T, Oda A, Sato H, Ozaki E, Tatsuta R, Yamamoto Y, Nakatochi M, Momozawa Y, Ohno K, Takashima N, Matsuo K, Itoh H
Eur J Clin Pharmacol · 2026 Jun · PMID 42319470 · Full text
PURPOSE: CYP3A4 and CYP3A5 are major drug‑metabolizing enzymes that require electrons supplied by P450 oxidoreductase (POR) for catalytic cycle. CYP3A expression is regulated by the nuclear receptors; constitutive andros...
PURPOSE: CYP3A4 and CYP3A5 are major drug‑metabolizing enzymes that require electrons supplied by P450 oxidoreductase (POR) for catalytic cycle. CYP3A expression is regulated by the nuclear receptors; constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Single-nucleotide polymorphisms (SNPs) of CYP3A5, CYP3A4, POR, CAR, and PXR have been documented to modulate CYP3A enzyme activity and/or expression. We performed a targeted candidate-gene-based analysis of selected CYP3A-related SNPs associated with variability in CYP3A activity in a relatively large sample of general Japanese population. METHODS: The study population was sampled from the general population participating in the J-MICC Study, and comprised 351 adults who underwent health checkups at Kyoto Prefectural University of Medicine, with genotyping of one SNP in CYP3A5, one SNP in CYP3A4, one SNP in POR, two SNPs in CAR, and six SNPs in PXR. 4β-hydroxycholesterol (4β-OHC) was used as endogenous biomarker of CYP3A activity. Plasma 4β-OHC levels were measured using ultra-high-performance liquid chromatography coupled to tandem mass spectrometry, and normalized to total cholesterol (TC). RESULTS: In univariate analyses, CYP3A5 expressors (*1/*1, *1/*3) exhibited approximately 25% higher median 4β-OHC/TC ratio than non-expressors (*3/*3) (p < 0.001). Carriers of the rs2242480 variant and POR*28 showed significantly higher 4β-OHC/TC ratios than their respective non-carriers (p < 0.001 and p = 0.044, respectively), whereas no significant differences were observed for CAR or PXR SNPs. Multiple linear regression analysis with demographic and clinical covariates as independent variables identified CYP3A5*3 and sex as independent predictors of 4β-OHC/TC ratio. CONCLUSION: These findings suggest that when assessing CYP3A activity using 4β-OHC/TC ratio as biomarker, only the CYP3A5*3 genotype may need to be considered.
Antimicrobial-induced hyponatremia: pathophysiological mechanisms, implicated agents, and clinical management strategies.
Liu T, Li R, Xu W … +6 more , Zhao F, Huang J, Liang L, Zhu Y, Zhao Z, Jin P
Eur J Clin Pharmacol · 2026 Jun · PMID 42313206 · Publisher ↗
BACKGROUND: Hyponatremia is a prevalent and serious electrolyte disorder affecting approximately 20% of hospitalized patients, significantly increasing morbidity and mortality. While common causes are well-documented, an...
BACKGROUND: Hyponatremia is a prevalent and serious electrolyte disorder affecting approximately 20% of hospitalized patients, significantly increasing morbidity and mortality. While common causes are well-documented, antimicrobial-induced hyponatremia is frequently underrecognized due to confounding infection-related factors. This review aims to systematically delineate the implicated antimicrobial agents, their underlying pathophysiological mechanisms, and clinical management strategies. METHODS: A comprehensive literature search was conducted via PubMed for studies published between January 1, 2000, and August 22, 2025. Data were synthesized to categorize drugs based on risk levels, mechanisms of action, and clinical outcomes. Backward citation tracking was employed to identify additional pertinent cases and mechanistic studies. RESULTS: The primary pathophysiological drivers identified are the syndrome of inappropriate antidiuresis (SIAD) and direct renal tubular dysfunction. High-risk agents include linezolid, trimethoprim-sulfamethoxazole and voriconazole. Other implicated agents include fluoroquinolones, vidarabine, rifabutin, azithromycin, aminoglycosides, colistin, nitrofurantoin and β-lactam antibiotics. Onset typically occurs within 2 to 14 days of therapy initiation. Key risk factors identified include advanced age (≥ 65 years), renal impairment, supratherapeutic dosing, large-volume hypotonic diluents, and concomitant use of diuretics or SSRIs. CONCLUSION: Antimicrobial-induced hyponatremia is an important clinical entity that necessitates a high index of suspicion, particularly in older adults and polymedicated patients. Management focuses on the prompt identification and withdrawal of the offending agent, followed by symptom-stratified sodium correction. This review provides a practical guide to mitigate risks. Future prospective studies are needed to elucidate the mechanisms and clinical characteristics of antimicrobial-induced hyponatremia. CLINICAL TRIAL NUMBER: Not applicable.
Evaluation of Vancomycin Therapeutic Drug Monitoring Strategies: Pharmacokinetic, Pharmacogenetic, and Clinical Perspectives in a Prospective, Real-World Cohort Study.
Kurt İ, Koçak EG, Şen M … +8 more , Mete B, Aygün G, Özdemir Ö, Günver MG, Dikmen Y, Tabak ÖF, Uydeş Doğan BS, Pala Kara Z
Eur J Clin Pharmacol · 2026 Jun · PMID 42310132 · Full text
PURPOSE: Vancomycin therapeutic drug monitoring is essential for optimizing efficacy and reducing the risk of vancomycin-associated acute kidney injury (VA-AKI). Although recent guidelines recommend the ratio of area und...
PURPOSE: Vancomycin therapeutic drug monitoring is essential for optimizing efficacy and reducing the risk of vancomycin-associated acute kidney injury (VA-AKI). Although recent guidelines recommend the ratio of area under the curve over 24 h to minimum inhibitory concentration (AUC/MIC)-based monitoring over trough concentration-based monitoring, differences between AUC/MIC estimation methods (e.g., pharmacokinetic equations and Bayesian approaches) may influence therapeutic classification in clinical practice. In addition, pharmacogenetic factors contributing to interindividual variability in vancomycin exposure remain incompletely characterized. METHODS: This prospective, single-center cohort study included adult patients who received intravenous vancomycin for at least 72 h between June 2024 and April 2025. Vancomycin trough and peak plasma concentrations were measured using an enzyme-linked immunosorbent assay. AUC/MIC values were calculated using pharmacokinetic equation and Bayesian method. Agreement in therapeutic classification between trough concentration-based and AUC/MIC-based monitoring was assessed. Associations between the rs2789047 genetic variant and relevant parameters were also evaluated. RESULTS: Thirty-six patients were included, of whom 38.9% developed VA-AKI. Despite strong correlations between trough concentration and AUC/MIC values (r = 0.84-0.87), substantial discordance in therapeutic classification was observed, with agreement rates of 63.9% for pharmacokinetic equation-based and 66.7% for Bayesian-based compared with trough concentration-based monitoring. In contrast, pharmacokinetic equation-based and Bayesian-based methods demonstrated strong concordance (86.1%). Higher trough concentrations and AUC/MIC values were significantly associated with VA-AKI (p < 0.001). Carriers of rs2789047 A-allele exhibited higher trough concentrations and reduced elimination rates. CONCLUSION: Trough concentration-based monitoring frequently misclassified vancomycin exposure compared with AUC/MIC-based approaches. Pharmacogenetic variability may further influence vancomycin exposure.
Glucose-lowering agents and hepatocellular carcinoma.
Lai SW, Liao KF
Eur J Clin Pharmacol · 2026 Jun · PMID 42303900 · Publisher ↗
Abstract loading — click title to view on PubMed.
Response to "Refining FIB-4-based risk stratification in adverse drug reactions".
Henze J, Goette L, Dormann H … +7 more , Schneider CV, Meeßen C, Knüppel-Ruppert A, Kriegisch-Stumpf A, Schwab M, Stingl JC, Just KS
Eur J Clin Pharmacol · 2026 Jun · PMID 42303897 · Full text
Abstract loading — click title to view on PubMed.
Severe hyperCKemia after levetiracetam with profound electrolyte disturbances.
Sato Y, Ishii N
Eur J Clin Pharmacol · 2026 Jun · PMID 42303833 · Publisher ↗
Abstract loading — click title to view on PubMed.
Association between anamorelin therapy and renal function in patients with cancer cachexia: a propensity score-matched retrospective study.
Sato A, Sumimoto T, Tanaka R … +3 more , Tatsuta R, Yoshikawa N, Itoh H
Eur J Clin Pharmacol · 2026 Jun · PMID 42298206 · Publisher ↗
PURPOSE: This study investigated the association between anamorelin (ANAM) treatment and longitudinal changes in renal function in patients with cancer cachexia. METHODS: This retrospective, single-centre, observational...
PURPOSE: This study investigated the association between anamorelin (ANAM) treatment and longitudinal changes in renal function in patients with cancer cachexia. METHODS: This retrospective, single-centre, observational cohort study reviewed electronic medical records of patients diagnosed with cancer cachexia. Renal function parameters-including blood urea nitrogen (BUN), serum creatinine, and estimated glomerular filtration rate (eGFR)-were compared between patients treated with ANAM and those not receiving ANAM. Propensity score matching was applied to adjust for baseline imbalance in patient characteristics. Renal deterioration was defined as ≥ 10% increase in BUN or ≥ 10% serum creatinine, or ≥ 10% decrease in eGFR. Cox proportional hazards models were applied to BUN, serum creatinine, and eGFR deterioration, respectively. RESULTS: After propensity score matching, ANAM treatment was associated with significantly greater improvements in serum creatinine and eGFR over an 8-week period compared with non-ANAM treatment. Multivariable Cox regression analyses demonstrated that ANAM use was independently associated with a reduction in risk of ≥ 10% increase in serum creatinine and ≥ 10% decrease in eGFR. Longitudinal analyses revealed improvements in renal function markers in the early phase after initiation of ANAM, followed by a gradual return toward baseline levels. CONCLUSION: ANAM treatment was associated with improvements in renal function markers and a lower risk of renal function deterioration in patients with cancer cachexia. These findings suggest that ANAM may potentially confer renoprotective effects in addition to its established therapeutic benefits for cachexia.
Acetaminophen exposure in an aging population and neurodegenerative outcomes.
Kim HJ, Jeong S
Eur J Clin Pharmacol · 2026 Jun · PMID 42297941 · Publisher ↗
Abstract loading — click title to view on PubMed.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe