International Journal Of Clinical Pharmacology And Therapeutics[JOURNAL]
Sun
200 papers
Prediction of paclitaxel-induced myelosuppression: Validation of a regression model using creatinine clearance and other risk factors obtained retrospectively in hospitalized cancer patients.
Hai Y, Liu Y
Int J Clin Pharmacol Ther · 2026 May · PMID 41914614 · Publisher ↗
OBJECTIVE: To develop a predictive model for paclitaxel (PTX)-induced moderate-to-severe myelosuppression in hospitalized cancer patients and to evaluate its accuracy through cross-validation. MATERIALS AND METHODS: A to...
OBJECTIVE: To develop a predictive model for paclitaxel (PTX)-induced moderate-to-severe myelosuppression in hospitalized cancer patients and to evaluate its accuracy through cross-validation. MATERIALS AND METHODS: A total of 348 cancer patients treated with PTX at Yingshang County People's Hospital between January 2022 and August 2025 were retrospectively reviewed. Clinical data from 278 patients were used to develop the model, including sex, age, underlying diseases, and baseline laboratory parameters at admission. Multivariate logistic regression was used to identify independent risk factors for moderate-to-severe myelosuppression and to construct the predictive model. The model was evaluated using receiver operating characteristic (ROC) curve analysis. An additional 70 patients were used for cross-validation to assess the model's accuracy. RESULTS: The incidence of PTX-induced moderate-to-severe myelosuppression was 32.37% in the 278-patient cohort. Multivariate analysis identified the following independent predictors: creatinine clearance rate (OR = 3.81, 95% CI: 1.853 - 7.836, p < 0.001), red blood cell count (OR = 2.69, 95% CI: 1.263 - 5.726, p = 0.01), hemoglobin (OR = 6.49, 95% CI: 2.431 - 17.328, p < 0.001), neutrophil count (OR = 3.196, 95% CI: 1.077 - 9.485, p = 0.036), and nutritional status (OR = 2.373, 95% CI: 1.008 - 5.586, p = 0.048). The predictive model incorporating these five factors demonstrated strong performance, achieving an AUC of 0.845, a sensitivity of 75.56%, and a specificity of 78.19%. Furthermore, cross-validation on an independent cohort of 70 patients confirmed a prediction accuracy of 84.29%. CONCLUSION: The developed predictive model demonstrates strong performance in assessing the risk of PTX-induced moderate-to-severe myelosuppression and may serve as a useful tool for early identification of high-risk patients, supporting clinical decision-making and personalized treatment strategies.
Postoperative infusion of dexmedetomidine for the prevention of postoperative delirium in elderly patients undergoing lung surgery: A randomized controlled trial.
Li F, Zhang W, Huo J … +2 more , Cheng L, Zhao R
Int J Clin Pharmacol Ther · 2026 Jun · PMID 41914613 · Publisher ↗
OBJECTIVE: This study aimed to investigate the effect of intravenous (IV) patient-controlled anesthesia (PCA) combined with dexmedetomidine (DEX) injections on reducing the risk of postoperative delirium (POD) in elderly...
OBJECTIVE: This study aimed to investigate the effect of intravenous (IV) patient-controlled anesthesia (PCA) combined with dexmedetomidine (DEX) injections on reducing the risk of postoperative delirium (POD) in elderly patients undergoing thoracoscopic lung surgery, hypothesizing a potential risk reduction. MATERIALS AND METHODS: Patients aged 65 years and older who underwent thoracoscopic lung surgery were assessed for eligibility. The participants were randomly assigned to either the test or control group. The test group received DEX through an IV PCA pump, consisting of 3 μg×kg sufentanil and 3 μg×kg DEX, while the control group received 3 μg×kg sufentanil. PCA parameters were standardized, including a total volume of 150 mL, a 2-mL bolus dose with a 15-minute lock-out period, and a background infusion rate of 2 mL/h. The primary outcome was the incidence of POD, which was evaluated twice daily for 7 days after surgery. The secondary outcomes included duration of POD, incidence of postoperative nausea and vomiting (PONV), postoperative hospitalization duration, pain assessment, and adverse events. RESULTS: A total of 287 patients were recruited. The incidence of POD in the control group was significantly higher (15.28 vs. 4.9%, p = 0.006). There were no significant differences in POD duration, PONV, or the length of hospital stay after operation between the two groups. The incidence of hypertension in the test group was significantly lower (p < 0.001), and no differences were found for other adverse events. CONCLUSION: IV patient-controlled DEX injections after major thoracoscopic lung surgery can reduce postoperative delirium.
Peripheral nerve regeneration and synergistic pharmacology using , lithium, and vitamin B12: The triple neuromodulatory axis hypothesis.
Radanović D, Rasulić L, Savić A … +4 more , Matić S, Micić D, Petrović P, Divac N
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41878942 · Publisher ↗
BACKGROUND: Peripheral nerve injuries (PNI) frequently result in incomplete functional recovery, creating a significant translational gap despite advances in surgical techniques. While (), lithium, and vitamin B12 have...
BACKGROUND: Peripheral nerve injuries (PNI) frequently result in incomplete functional recovery, creating a significant translational gap despite advances in surgical techniques. While (), lithium, and vitamin B12 have individually demonstrated promising neuromodulatory and neurotrophic properties -targeting axonal growth, myelination, and neuroprotection - no existing experimental model has investigated their combined synergistic potential. This lack of integrated approach represents a major barrier to developing effective multimodal therapies. HYPOTHESIS: We propose a "triple neuromodulatory axis" hypothesis: that the combined administration of , lithium, and vitamin B12 will exert a synergistic effect on peripheral nerve regeneration. This synergy is mechanistically driven by the agents' convergence on three vital pathways: neurotrophic signaling (TrkA/ERK), glial modulation (GSK-3β/β-catenin), and metabolic/methylation support. The coordinated action of this axis is hypothesized to ensure simultaneous initiation of axonal growth, rapid Schwann cell proliferation, and sustained myelination. Translational rationale: The convergence of these mechanisms suggests that the triple axis, when tested in appropriate in vivo models of nerve injury, will yield superior functional outcomes (e.g., Sciatic Functional Index) and histological repair (e.g., myelin density and axon count) compared to standard treatments or mono-treatments. CONCLUSION: The triple neuromodulatory axis provides a testable translational framework for designing future multi-arm studies aimed at validating a novel, synergistic pharmacological strategy for enhancing neurorepair in diabetic and post-traumatic neuropathies.
Beneficial effects of dexmedetomidine with sevoflurane inhalation in abdominal surgery: Quality of anesthesia, intestinal flora, and serum pain mediators.
Pan Q, Mao L, Lv Q
Int J Clin Pharmacol Ther · 2026 Jul · PMID 41878941 · Publisher ↗
OBJECTIVE: To evaluate the effects of anesthesia with dexmedetomidine (DEX) and closed-loop target-controlled inhalation of sevoflurane on the intestinal flora and levels of serum pain mediators in patients undergoing ab...
OBJECTIVE: To evaluate the effects of anesthesia with dexmedetomidine (DEX) and closed-loop target-controlled inhalation of sevoflurane on the intestinal flora and levels of serum pain mediators in patients undergoing abdominal surgery. MATERIALS AND METHODS: A cohort of 100 patients who had received abdominal surgery in the period February 2022 to March 2024 were recruited in this retrospective study. The observational group (n = 50) received anesthesia with DEX plus closed-loop target-controlled inhalation of sevoflurane, and the control group (n = 50) received anesthesia with DEX alone. Inter-group comparisons were made for sex, age, etiology, and educational level and for the quality of anesthesia (anesthesia recovery time and induction time), changes in the intestinal flora (Shannon index and Simpson index) and levels of serum pain mediators (prostaglandin E (PGE), tumor necrosis factor-α (TNF-α), and 5-hydroxytryptamine (5-HT)) before anesthesia and 5 minutes after anesthesia induction. RESULTS: The anesthesia recovery and induction time were significantly shorter in the observational group than in the control group (p < 0.05). At 5 minutes after anesthesia induction, both the Shannon index and Simpson index were significantly lower in the control group than in the observation group (p < 0.05), and the levels of PGE, TNF-α, and 5-HT were also significantly lower in the observation group (p < 0.05). CONCLUSION: Evidence was provided showing that anesthesia with DEX plus closed-loop target-controlled inhalation with sevoflurane improves the quality of the anesthesia, reduces the levels of serum pain mediators, and has potentially beneficial effects on the intestinal flora in patients undergoing abdominal surgery.
Systemic bismuth absorption and safety of the gastric mucosal protective bismuth potassium citrate, administered as granules and tablets in healthy Chinese and validation of a new, ICP-MS bismuth assay.
Lv X, Wu J, Ye S … +5 more , Wang Q, Gan S, Pi J, Xiong Y, Zhang N
Int J Clin Pharmacol Ther · 2026 Jun · PMID 41878940 · Publisher ↗
BACKGROUND: The mucosal protective agent, bismuth potassium citrate, is used for treatment of chronic gastritis and gastric stress conditions, including heartburn and acid reflux. OBJECTIVES: 1) To establish and validate...
BACKGROUND: The mucosal protective agent, bismuth potassium citrate, is used for treatment of chronic gastritis and gastric stress conditions, including heartburn and acid reflux. OBJECTIVES: 1) To establish and validate a new inductively coupled mass spectrometry (ICP-MS) analytical method for the determination of bismuth metal in human plasma; and 2) to determine the systemic absorption and safety characteristics of bismuth following the administration of bismuth potassium citrate granules (test drug) and bismuth potassium citrate tablets (reference drug) in healthy Chinese subjects. MATERIALS AND METHODS: A single-center, randomized, open-label, two-drug, single-dose, two-cycle, double-crossover pharmacokinetics study was carried out in a cohort of 24 healthy adult subjects in the fasting state. Subjects meeting the inclusion criteria were randomly assigned to the first cycle in ascending order of screening number obtained prior to dosing. The randomization table assigned subject either to the TR-group (test-reference cycle) or the RT group (reference-test cycle) where each group contained a total of 12 subjects. Subjects recruited but not completing the study, or in whom the data sets were incomplete, were not replaced. Using this study design, all subjects received a single dose of both preparations in the fasting state whereby 12 subjects received the drugs in the order RT and 12 subjects in the order TR, with a washout period of 7 days between each drug administration cycle, respectively. RESULTS: Pharmacokinetic parameters (concentration maximum (C), AUC, and area under the concentration-time curve to infinity (AUC) were analyzed using a linear mixed-effects model after natural log transformation. The lower limit of the 90% confidence intervals for the geometric mean ratio (test preparation/reference preparation) were below 100%, and the bioavailability of the test formulation (granules) was markedly superior to that for the reference formulation (tablets) where values for C, AUC, and AUC after natural log transformation were 5.44, 12.82, 10.86, 22.44, and 13.79%, 27.42%, respectively. The systemic absorption of bismuth metal from the granules was not greater than that for the tablets. CONCLUSION: Although the bioavailability of the granules was markedly superior to tablets, the systemic absorption of bismuth metal from the two formulations was similar, and there was no evidence for a difference in the safety characteristics.
Can tiotropium add-on inhalation revolutionize therapy in elderly asthmatic patients? A treatable traits approach towards successful aging.
Ishiura Y, Nomura S, Ohkura N … +3 more , Hara J, Fujimura M, Ito T
Int J Clin Pharmacol Ther · 2026 Jun · PMID 41841282 · Publisher ↗
BACKGROUND: The population of elderly patients with asthma is increasing, resulting in serious health problems because of hospitalization and high mortality rate. Furthermore, several recent studies have shown that progr...
BACKGROUND: The population of elderly patients with asthma is increasing, resulting in serious health problems because of hospitalization and high mortality rate. Furthermore, several recent studies have shown that progressive airflow limitation may worsen cognitive dysfunction and contribute to poor asthma control. Maintaining good respiratory function is therefore important in the elderly in order to achieve a satisfactory quality of life. MATERIALS AND METHODS: A 12-week, open-label, cross-over study was conducted in elderly patients with asthma to investigate the effect of 5 μg/day tiotropium bromide (TIO) add-on therapy administered using a soft mist inhaler (SMI), in addition to a dosage of 500/20 µg/day fluticasone propionate/formoterol fumarate (FP/FM) treatment and to compare the effects of treatment with those following the administration of 500/20 µg/day FP/FM alone. The trial design thus entailed a 4-week run-in period and two 4-week treatment periods. RESULTS: A total of 21 patients aged over 65 years with stable bronchial asthma were recruited in the study. Forced expiratory volume in 1 second values after the treatment period with FP/FM and TIO add-on therapy were significantly higher than those after the run-in period (p < 0.01). CONCLUSION: TIO add-on therapy FP/FM treatment using an SMI in elderly patients with asthma improved lung function parameters demonstrating, the value of TIO add-on therapy as a treatable traits option for improving quality of life and achieving successful aging in this population.
Acute arsenic poisoning from realgar water: Case series from Guilin, China.
Fu YF, Xu HZ, Long X … +8 more , Liao QQ, Huang HL, Deng K, Jiang YJ, Tang GR, Tang SP, Tang J, Qin D
Int J Clin Pharmacol Ther · 2026 Jun · PMID 41841281 · Publisher ↗
BACKGROUND: The inappropriate use of Traditional Chinese Medicine (TCM) poses significant health risks. Realgar (AsS), an arsenic-containing mineral traditionally consumed during China's Dragon Boat Festival, may induce...
BACKGROUND: The inappropriate use of Traditional Chinese Medicine (TCM) poses significant health risks. Realgar (AsS), an arsenic-containing mineral traditionally consumed during China's Dragon Boat Festival, may induce acute toxicity following ingestion. MATERIALS AND METHODS: This case series describes 8 patients (age: 1 - 80 years), including 2 children, with clinically confirmed acute arsenic poisoning subsequent to Dragon Boat Festival ingestion of realgar-containing water. We systematically evaluated clinical manifestations, laboratory parameters, and environmental arsenic concentrations. Urinary arsenic quantification was performed in all cases, with intravenous 2,3-dimercaptopropane sulfonic acid (DMPS) sodium salt initiated as chelation therapy. RESULTS: All patients developed gastrointestinal manifestations (nausea, vomiting, and diarrhea) within 5 - 14 days post exposure, accompanied by biochemical evidence of hepatic dysfunction. Laboratory analyses confirmed elevated urinary arsenic concentrations (> 0.032 mg/L) and identified arsenic contamination in drinking water (> 0.01 mg/L), with both measures exceeding established safety thresholds. Multi-organ dysfunction syndrome (MODS) was observed in 3 patients. All cases demonstrated a favorable clinical response to intravenous DMPS sodium salt chelation therapy, achieving clinical improvements and subsequent discharge. CONCLUSION: This case series documented acute arsenic toxicity secondary to realgar consumption in both adults and children. The findings underscore the critical need for targeted public health education initiatives and enhanced regulatory oversight regarding traditional medicinal practices, particularly during cultural festivals. Furthermore, they emphasize the necessity for heightened clinical vigilance in the prompt diagnosis and management of arsenic poisoning associated with traditional cultural practices.
Network pharmacology and bioinformatics analysis of the multi-target immune-inflammatory mechanisms of Shengma Gegen decoction in chronic urticaria.
Hu M, Ma Y, Li J … +1 more , Wu J
Int J Clin Pharmacol Ther · 2026 Jul · PMID 41841280 · Publisher ↗
BACKGROUND: Chronic urticaria (CU) is a refractory, long-course skin disorder involving multifactorial and complex pathophysiology. Although Shengma Gegen decoction (SMGG) shows clinical benefit, its mechanistic basis re...
BACKGROUND: Chronic urticaria (CU) is a refractory, long-course skin disorder involving multifactorial and complex pathophysiology. Although Shengma Gegen decoction (SMGG) shows clinical benefit, its mechanistic basis remains unclear. AIMS: To elucidate the multitarget, multipathway mechanisms of SMGG in CU and to prioritize key targets and pathways for subsequent experimental validation. MATERIALS AND METHODS: We integrated network pharmacology and bioinformatics using TCMSP, UniProt, GeneCards, and OMIM. A total of 126 bioactive compounds and 216 putative targets were identified. Enrichment analyses (including KEGG) were performed, immune-infiltration patterns were assessed, and molecular docking plus molecular-dynamics simulations evaluated ligand-target interactions. RESULTS: Key regulatory targets were highlighted - MMP9, IL6, AKT1, IL1B and TNF - with strong associations to inflammatory and immune regulation. KEGG analysis prioritized AGE-RAGE, TNF, and IL-17 pathways. Immune-infiltration analysis suggested that SMGG may modulate the Th1/Th2 balance. Docking and dynamics demonstrated stable binding and plausible dynamic interactions between representative active components and the prioritized targets. DISCUSSION: These findings support a multi-target, multi-pathway mode of action for SMGG in CU, aligning inflammatory signaling and immune modulation. As an in-silico study, the results provide hypotheses that warrant rigorous in-vitro and in-vivo validation. CONCLUSION: SMGG may ameliorate CU by coordinately regulating inflammatory pathways (AGE-RAGE, TNF, IL-17) and immune balance via core targets (MMP9, IL6, AKT1, IL1B, TNF). The study offers a mechanistic basis and target/pathway prioritization to guide future experimental work and the modernization of traditional formulations.
Vancomycin-induced acute kidney injury in a type 2 diabetes patient with augmented renal clearance: A case report and dosing strategy implications.
Wang LF, Zhou J, Chen R
Int J Clin Pharmacol Ther · 2026 May · PMID 41793706 · Publisher ↗
Vancomycin-induced acute kidney injury (AKI) is a well-documented adverse effect, particularly in high-risk populations such as patients with type 2 diabetes mellitus (T2DM) and augmented renal clearance (ARC). However,...
Vancomycin-induced acute kidney injury (AKI) is a well-documented adverse effect, particularly in high-risk populations such as patients with type 2 diabetes mellitus (T2DM) and augmented renal clearance (ARC). However, optimal dosing strategies for diabetic patients with ARC remain unclear, increasing the risk of nephrotoxicity. A 36-year-old male with newly diagnosed T2DM (HbA1c 11.6%) and ARC (baseline estimation of glomerular filtration rate (eGFR) 270 - 301 mL/min/1.73m) developed AKI following high-dose vancomycin therapy (1.5g q8h) for a methicillin-resistant (MRSA) abscess. Despite initially subtherapeutic trough levels (8.83 μg/mL), the patient experienced AKI (serum creatinine: 195 μmol/L; eGFR 36.1 mL/min) coinciding with a toxic trough level (75.84 μg/mL) on day 7 after vancomycin administration. AKI resolved after vancomycin discontinuation and aggressive hydration. Diabetic patients with ARC are at increased risk of vancomycin-induced AKI, even with subtherapeutic troughs. Close renal function monitoring, individualized dosing, and consideration of AUC-based protocols or alternative antibiotics (e.g., linezolid) are essential for mitigating nephrotoxicity. Further pharmacokinetic studies in this population are warranted to optimize therapeutic outcomes.
Antihypertensive drug-induced adverse events in patients aged 80 years and older: A retrospective analysis using the Japanese Adverse Drug Event Report Database.
Matsushima R, Hashiguchi M, Shiga T
Int J Clin Pharmacol Ther · 2026 Jun · PMID 41723747 · Publisher ↗
BACKGROUND: This study aimed to evaluate major antihypertensive drugs associated with adverse events (AEs) in patients aged ≥ 80 years using the Japanese Adverse Drug Event Report (JADER) database. MATERIALS AND METHODS:...
BACKGROUND: This study aimed to evaluate major antihypertensive drugs associated with adverse events (AEs) in patients aged ≥ 80 years using the Japanese Adverse Drug Event Report (JADER) database. MATERIALS AND METHODS: We utilized the JADER database (April 2004 - September 2023). Patients aged ≥ 80 years who were taking angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), dihydropyridine calcium channel blockers (CCBs), β-blockers, and thiazide/thiazide-like diuretics as "suspected agents" were included. Eight AEs were extracted for analysis. Adjusted reporting odds ratios (aRORs) and 95% confidence intervals (CIs) were calculated using sex as a covariate. RESULTS: The highest aROR for syncope/loss of consciousness was associated with β-blockers (2.57 (95% CI 1.84 - 3.58)), followed by CCBs (2.56 (95% CI 1.95 - 3.36)). Only CCBs showed a significant associated with falls (1.58 (95% CI 1.10 - 2.27)). The highest aROR for bradycardia was associated with β-blockers (18.20 (95% CI 15.64 - 21.18)). The highest aROR for renal failure was for diuretics (2.71 (95% CI 1.83 - 4.02)), followed by ACEIs/ARBs (2.26 (95% CI 1.97 - 2.58)). Electrolyte abnormalities had the greatest aROR for hyperkalemia with ACEIs/ARBs (15.34 (95% CI 13.70 - 17.18)) and for hypokalemia and hyponatremia with diuretics (15.72 (95% CI 11.30 - 21.87), 27.40 (20.27 - 37.0)). Only CCBs showed a significant associated with edema (4.00 (95% CI 2.32 - 6.91)). CONCLUSION: This study, which employed the JADER database, identified specific AEs associated with drug use in patients aged ≥ 80 years. These AEs included syncope/loss of consciousness associated with β-blockers or CCBs as well as falls and edema associated with CCBs.
Iodixanol-induced acute kidney injury and multi-organ complications via alternative excretion: A case report and mechanism exploration.
Li L, Yang L, Wu H … +2 more , Chen L, Jiang Z
Int J Clin Pharmacol Ther · 2026 Jun · PMID 41723746 · Publisher ↗
OBJECTIVE: To report a rare case of vicarious contrast material excretion (VCME) following iodixanol administration, leading to acute kidney injury (AKI) and multi-organ complications, and to explore the underlying mecha...
OBJECTIVE: To report a rare case of vicarious contrast material excretion (VCME) following iodixanol administration, leading to acute kidney injury (AKI) and multi-organ complications, and to explore the underlying mechanisms. CASE PRESENTATION: A 71-year-old female underwent lower limb venography with intravenous iodixanol. Post-procedure, she developed AKI, followed by acute pancreatitis, hepatic hemorrhage, and hemoperitoneum. Imaging revealed contrast accumulation in the gallbladder and biliary tract, consistent with VCME. INTERVENTION AND OUTCOME: The patient was managed with hemodialysis, octreotide, transfusion, and supportive care. Laboratory and imaging improvements were observed by day 22, with successful discharge. CONCLUSION: This case highlights the potential for iodixanol to induce VCME and subsequent multi-organ injury in the setting of AKI. Enhanced preoperative risk assessment, postoperative monitoring, and multidisciplinary management are essential for mitigating such rare but severe complications.
A randomized, open-label, single-dose study to evaluate the safety and pharmacokinetics of two formulations containing 40 mg of fexuprazan in healthy Korean subjects.
Hur J, Lee JA, Park H … +5 more , Choi Y, Chae J, Kwak YG, Moon SJ, Kim MG
Int J Clin Pharmacol Ther · 2026 May · PMID 41723745 · Publisher ↗
OBJECTIVE: To evaluate the pharmacokinetics and safety of two 40-mg fexuprazan formulations. MATERIALS AND METHODS: This study was an open-label, randomized, single-dose, crossover bioequivalence trial in healthy subject...
OBJECTIVE: To evaluate the pharmacokinetics and safety of two 40-mg fexuprazan formulations. MATERIALS AND METHODS: This study was an open-label, randomized, single-dose, crossover bioequivalence trial in healthy subjects. 24 subjects were randomized to receive either the test formulation, tablet A (40 mg fexuprazan), or the reference formulation, tablet B (40 mg fexuprazan), with crossover administration. Plasma samples were collected up to 48 hours post-dose and analysed for fexuprazan using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Individual pharmacokinetic parameters were derived by noncompartmental analysis. Safety was evaluated throughout the study. RESULTS: 22 subjects completed the study and were included in the pharmacokinetic analysis. Geometric mean values of area under the plasma concentration-time curve from time zero to the last quantifiable concentration (AUC) was 380.17 and 390.33 ng×h/mL for the test and reference formulations, respectively. Geometric mean values of maximum plasma concentration (C) were 29.36 and 31.65 ng/mL for the test and reference formulations, respectively. The 90% confidence intervals (CIs) for the test/reference geometric mean ratios of AUC and C were 0.9098 - 1.0427 and 0.8665 - 0.9931, respectively. All adverse events were mild, and no serious adverse events occurred. CONCLUSION: The novel 40-mg fexuprazan formulation (tablet A) was demonstrated to be bioequivalent to the initially developed formulation (tablet B), with comparable systemic exposure (AUC) and peak concentration (C). Both formulations were well tolerated, with no clinically meaningful differences in adverse event profiles.
Low-dose lamotrigine co-administration decreases quetiapine plasma concentrations: Effect of -161C>T polymorphism in Japanese patients with depression.
Suzuki T, Nagai G, Mihara K … +5 more , Tomori Y, Kagawa S, Nakamura A, Nemoto K, Kondo T
Int J Clin Pharmacol Ther · 2026 May · PMID 41723744 · Publisher ↗
OBJECTIVES: Previous findings showing that lamotrigine co-administration decreases serum quetiapine concentrations were based solely on group comparisons using therapeutic drug monitoring databases. The present prospecti...
OBJECTIVES: Previous findings showing that lamotrigine co-administration decreases serum quetiapine concentrations were based solely on group comparisons using therapeutic drug monitoring databases. The present prospective study examined the effects of lamotrigine co-administration on plasma quetiapine concentrations in Japanese patients with depression and in relation to polymorphisms of UGT1A2 and UGT2B7, enzymes responsible for lamotrigine metabolism. MATERIALS AND METHODS: 14 patients with depression were recruited in the study. They had been treated with immediate-release quetiapine 200, 400, or 700 mg/d. Lamotrigine was co-administered in all patients over a period of 8 weeks where the final doses of lamotrigine were 75 mg/d in 2 subjects taking valproate and 100 mg/d in 12 subjects not taking valproate. Blood samples were collected before and 2, 4, and 8 weeks after commencing lamotrigine co-administration. Quetiapine and lamotrigine concentrations in plasma were measured using LC/MS/MS. The genotypes of the 142T>G, -161C>T, and 372A>G polymorphisms were identified using real-time PCR analysis. RESULTS: The mean plasma concentration of quetiapine 8 weeks after lamotrigine treatment was significantly lower than that prior to the administration (p < 0.05). The mean percentage reduction in quetiapine concentration was significantly greater in subjects carrying the C/T and T/T genotypes when compared to those carrying the C/C genotype in respect to the -161C>T polymorphism (p < 0.05). CONCLUSION: The present study provides evidence that low-dose lamotrigine co-administration decreases plasma quetiapine concentrations in Japanese patients with depression and that the magnitude of this effect differs between genotypes of the -161C>T polymorphism.
Adenosine-2A agonists: Positioning as functional contrast agents in diagnostic cardiology.
Woodcock-Kloberdanz BG
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41670231 · Publisher ↗
Abstract loading — click title to view on PubMed.
GLP-1 receptor agonists as adjunct therapy in hidradenitis suppurativa: A hypothesis.
Feily A
Int J Clin Pharmacol Ther · 2026 May · PMID 41582649 · Publisher ↗
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Hemoglobin A1c levels in patients with type 2 diabetes mellitus receiving oral semaglutide with versus without proton pump inhibitors: An exploratory study.
Matsunuma S, Hirota Y, Yoshimoto K
Int J Clin Pharmacol Ther · 2026 May · PMID 41582648 · Publisher ↗
OBJECTIVE: Oral semaglutide contains salcaprozate sodium, which promotes the opening of epithelial tight junctions and increases gastric pH to prevent its degradation; these actions together improve absorption. Proton pu...
OBJECTIVE: Oral semaglutide contains salcaprozate sodium, which promotes the opening of epithelial tight junctions and increases gastric pH to prevent its degradation; these actions together improve absorption. Proton pump inhibitors (PPIs) increase gastric pH. However, it is unclear whether PPIs affect the absorption of semaglutide and may therefore enhance the blood glucose lowering effect of semaglutide or affect the reduction of hemoglobin A1c (HbA1c). Therefore, this study investigated differences in HbA1c changes and adverse events between those with and without PPI co-administration. MATERIALS AND METHODS: This single-center retrospective study included patients with type 2 diabetes who received oral semaglutide. Patients were categorized into two groups: those on treatment with PPI (w/PPI) and those not on treatment with PPI (without PPI (w/o PPI)). The primary outcome was the change in HbA1c levels at 52 weeks, while the secondary outcomes included changes at 26 weeks and the incidence of adverse events. RESULTS: A total of 66 patients were included. HbA1c reduction at 52 weeks was significantly greater in the w/PPI group (-1.56 ± 0.37%) than in the w/o PPI group (-1.08 ± 0.76%, p = 0.024). The incidences of adverse events were 24.0% and 31.7% in the w/PPI and w/o PPI groups, respectively (p = 0.502). CONCLUSION: HbA1c reduction at 52 weeks was significantly greater in the PPI co-administration group than in the group without PPI. Future research should include larger sample sizes and pharmacokinetic studies to clarify the clinical implications and interactions between oral semaglutide and PPIs.
Epidemiological characteristics of severe skin adverse reactions caused by immune checkpoint inhibitors based on case reports.
Tang SN, Ma XW, Zhang XY … +6 more , Zhang NN, Wang F, Ye FL, Chen NN, Yang P, Zhu NN
Int J Clin Pharmacol Ther · 2026 May · PMID 41582647 · Publisher ↗
OBJECTIVE: To investigate the epidemiological characteristics of severe cutaneous adverse reactions (cirAEs) induced by immune checkpoint inhibitors (ICIs) and to provide evidence for the rational clinical use of ICIs an...
OBJECTIVE: To investigate the epidemiological characteristics of severe cutaneous adverse reactions (cirAEs) induced by immune checkpoint inhibitors (ICIs) and to provide evidence for the rational clinical use of ICIs and pharmacovigilance for cutaneous toxicities. MATERIALS AND METHODS: We systematically searched the PubMed, MEDLINE, EMBASE, CNKI, and Wanfang databases using keywords including "immune checkpoint inhibitors," "cutaneous adverse reactions," "cutaneous toxicity," "induced," and "case," and their combinations to identify detailed case reports on cirAEs. Data on patient demographics (sex and age), primary cancer type, ICI use, time to cirAE onset, cirAE severity grading, and reaction classification were extracted. Descriptive statistics, co-occurrence analysis of clinical manifestations, and the Apriori algorithm were employed to analyze cirAE patterns. RESULTS: The analysis included a total of 120 articles involving 126 patients (male: 80; female: 46) with a mean age of 63.05 ± 11.85 years. The highest incidence was observed in patients aged 60 - 69 years. The primary cancers were predominantly non-small cell lung cancer and melanoma. Programmed death 1 (PD-1) inhibitors were the most commonly used therapeutic agents. The median time to onset was 15 - 28 days. Most cases were classified as severe Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). CONCLUSION: Healthcare professionals must remain vigilant for severe cirAEs and ensure timely diagnosis and management to safeguard patient safety during ICI therapy.
Pharmacokinetics and safety of a telmisartan/amlodipine/rosuvastatin fixed-dose combination tablet compared to co-administration of telmisartan/amlodipine and rosuvastatin in healthy Korean male volunteers.
Moon SJ, Park JS, Kwak YG … +1 more , Kim MG
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41553169 · Publisher ↗
OBJECTIVE: This study was conducted to compare the single-dose pharmacokinetic and safety profiles of JLP-1401 (fixed-dose combination (FDC) of telmisartan/amlodipine/rosuvastatin) to those of each constituent co-adminis...
OBJECTIVE: This study was conducted to compare the single-dose pharmacokinetic and safety profiles of JLP-1401 (fixed-dose combination (FDC) of telmisartan/amlodipine/rosuvastatin) to those of each constituent co-administered in healthy Korean male volunteers. MATERIALS AND METHODS: A total of 40 healthy Korean subjects participated in an open-label, randomized, single-dose, 4-period crossover study. During each treatment period, the subjects received the test drug (FDC tablet of telmisartan/amlodipine/rosuvastatin 80 mg/10 mg/20 mg) or reference drug (co-administration of telmisartan/amlodipine FDC tablet and rosuvastatin tablet). Plasma samples were collected pre dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, 48, and 72 hours post dose to evaluate pharmacokinetic profiles. Safety was assessed by the evaluation of adverse events (AEs), laboratory assessments, 12-lead electrocardiograms, physical examinations, and vital sign measurements. RESULTS: The geometric least-square mean ratios and their 90% confidence intervals of AUC and C were 1.01 (0.94 - 1.07) and 0.83 (0.72 - 0.95) for telmisartan, 1.01 (0.99 - 1.04) and 1.03 (1.01 - 1.06) for amlodipine, and 1.03 (0.98 - 1.08) and 0.94 (0.85 - 1.04) for rosuvastatin, respectively. All AEs were of mild or moderate intensity, and there were no significant differences in the incidence of AEs between the treatments. DISCUSSION AND CONCLUSION: The pharmacokinetic profiles of the test and reference drugs were within the bioequivalent criteria, and both drugs were safe and well tolerated.
Pharmacokinetics of the potassium-competitive acid blocker tegoprazan administered by the oral route in healthy Mexicans.
Carrasco-Portugal MDC, González-Hernández GV, López-Cartagena PD … +1 more , Flores-Murrieta FJ
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41553168 · Publisher ↗
BACKGROUND: Tegoprazan is a potassium channel inhibitor with an anti-acid secretion effect. It is metabolized by CYP3A4, a cytochrome enzyme the occurrence of which in the Mexican population, differs from that in some ot...
BACKGROUND: Tegoprazan is a potassium channel inhibitor with an anti-acid secretion effect. It is metabolized by CYP3A4, a cytochrome enzyme the occurrence of which in the Mexican population, differs from that in some other populations. Since the efficacy and safety studies on tegoprazan have been conducted in Koreans, it is of considerable clinical importance to establish whether differences exist in CYP3A4 metabolism between the two populations. AIMS: To evaluate the oral pharmacokinetics of tegoprazan and to compare the pharmacokinetic data with those reported in the literature for Koreans. MATERIALS AND METHODS: The investigation was carried out in a cohort of 20 healthy Mexican volunteers (11 women and 9 men), who were administered a dose of 50 mg after fasting for at least 10 hours. Blood samples were taken at selected time points over 24 hours, and tegoprazan plasma concentrations measured using high-performance liquid chromatography. Pharmacokinetic parameters were compared to those in Koreans reported in the literature. RESULTS: Tegoprazan is rapidly absorbed from the gastrointestinal tract reaching C at ~ 1 hour post dose (t) and is removed from the circulation with an average half-life of ~ 4 hours. The pharmacokinetic parameters obtained were similar to those obtained in Koreans including elimination half-life, maximum tegoprazan concentrations, and oral bioavailability. DISCUSSION AND CONCLUSION: Since no clinically relevant pharmacokinetic differences were observed in the pharmacokinetics of tegoprazan, a substrate for CYP3A4, between Mexicans and Koreans, it is concluded that the efficacy and safety data for tegoprazan obtained in Koreans will be valid in the Mexican population.
Effect of AST-120 treatment discontinuation and serum albumin on free and bound indoxyl sulphate in end-stage kidney disease.
Yoshida T, Tsujimoto M, Fujioka H … +14 more , Irie Y, Kawakami S, Nakatani S, Iso A, Sugiyama A, Miyake M, Sumino K, Tanaka R, Oda T, Furukubo T, Izumi S, Yamakawa T, Minegaki T, Nishiguchi K
Int J Clin Pharmacol Ther · 2026 Apr · PMID 41540819 · Publisher ↗
OBJECTIVE: To examine the effects of the oral uremic toxin absorbent AST-120 on the concentration of free and protein-bound indoxyl sulphate (IS) and to assess the effects of serum albumin in end-stage kidney disease (ES...
OBJECTIVE: To examine the effects of the oral uremic toxin absorbent AST-120 on the concentration of free and protein-bound indoxyl sulphate (IS) and to assess the effects of serum albumin in end-stage kidney disease (ESKD) patients undergoing hemodialysis. MATERIALS AND METHODS: The study enrolled 37 ESKD patients who initiated hemodialysis at the Shirasagi Hospital. Serum free and bound IS concentrations were measured before the first of 4 hemodialysis sessions and after the last hemodialysis 7 days later. The cohort contained a subgroup of patients in whom AST-120 treatment (6 g/day) was discontinued immediately prior to the first hemodialysis and a subgroup not treated with AST-120. Clinical characteristics were obtained from electronic medical records. RESULTS: Discontinuation in AST-120 treatment prior to dialysis resulted in marked but highly variable increases in IS concentrations, measured 7 days later, where the efficiency of dialysis of IS was dependent on the serum albumin concentration. DISCUSSION: The observation that the percentage change in IS concentration was significantly higher after discontinuation of AST-120 compared to those not receiving AST-120 was unexpected as was the finding of a high inter-patient variability in IS concentrations before and after hemodialysis. The effects of a discontinuation in AST-120 administration can be interpreted as a rebound in the systemic absorption of indole precursors, but the source of variability in IS concentrations was unclear. Although there are important limitations in this investigation, the report presents valid and valuable data on free and albumin-bound IS concentrations during hemodialysis and AST-120 treatment as well as measurements of serum albumin concentrations in the group of largely elderly subjects. CONCLUSION: AST-120 in ESKD patients has profound effects on the disposition of IS. There are important sources of variability having a possible marked effect on the concentration of IS in patients with chronic kidney disease. Discontinuing AST-120 treatment before hemodialysis, a practice in Japan to avoid the "off-label" administrations of the agent, will result in high and variable concentrations of uremic toxins such as IS. The consequences of this effect will include progression of the disease and the occurrence of cardiovascular and neurological degeneration.
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