International Journal Of Clinical Pharmacology And Therapeutics[JOURNAL]
Sun
200 papers
Colistin-induced neurotoxicity in a young patient with multidrug-resistant bacteremia: A case report.
Momcilovic M, Siroglavic M, Pasara V … +5 more , Mustapic V, Nedeljkovic V, Kovac AZ, Situm I, Lovric D
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41508882 · Publisher ↗
OBJECTIVE: To present a case of suspected colistin-induced neurotoxicity, likely resulting from drug accumulation during treatment of multidrug-resistant (PA) bacteremia. CASE REPORT: An 18-year-old female with no prior...
OBJECTIVE: To present a case of suspected colistin-induced neurotoxicity, likely resulting from drug accumulation during treatment of multidrug-resistant (PA) bacteremia. CASE REPORT: An 18-year-old female with no prior medical history was admitted to the coronary care unit with fulminant myocarditis, requiring mechanical circulatory support and ultimately left-ventricular assist device implantation. Three weeks later, she developed PA bacteremia. Despite multiple targeted antibiotic regimens, PA persisted in subsequent blood cultures. Colistimethate sodium (CMS) was initiated at 2 × 4.5 MIU, the recommended dose according to serum creatinine-based renal function (eGFR ~ 133 mL/min/1.73m). On day 4, the patient developed an acute confusional state with hallucinations. While serum creatinine remained stable, cystatin C and 24-hour urine clearance indicated impaired renal function (eGFR ~ 32 mL/min/1.73m). As therapeutic drug monitoring (TDM) was unavailable, the CMS dose was reduced to 2 × 2.5 MIU based on cystatin C-estimated renal function, leading to resolution of neurological symptoms within 3 days. CMS was continued for 10 days, leading to improved inflammatory markers and clinical stabilization. CONCLUSION: Colistin-induced neurotoxicity should be considered in patients with new-onset neuropsychiatric symptoms, particularly in the setting of renal dysfunction or high cumulative exposure. Reliance on serum creatinine alone may misrepresent renal function; incorporation of cystatin C or urine clearance can improve dosing accuracy and reduce toxicity risk. When therapeutic alternatives are limited, dose reduction rather than discontinuation may be an appropriate strategy. Broader implementation of TDM is essential to optimize dosing and minimize adverse outcomes in clinical practice.
Impact of extracorporeal membrane oxygenation on antituberculosis drug concentrations: A case study and pharmaceutical care strategies.
Xu Y, Lv F, Yu X
Int J Clin Pharmacol Ther · 2026 Apr · PMID 41508881 · Publisher ↗
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides life support for critically ill tuberculosis (TB) patients. However, during ECMO therapy, significant fluctuations in the plasma concentration of anti-TB dr...
BACKGROUND: Extracorporeal membrane oxygenation (ECMO) provides life support for critically ill tuberculosis (TB) patients. However, during ECMO therapy, significant fluctuations in the plasma concentration of anti-TB drugs occur due to drug adsorption in the ECMO circuit, hemodilution, and metabolic disturbances. MATERIALS AND METHODS: This single-case study monitored the plasma concentration of anti-TB drugs in a TB patient supported by ECMO. RESULTS: The differences in peak plasma concentrations (C) measured at the end of ECMO support vs. 7 days after ECMO withdrawal were as follows: isoniazid (66%), linezolid (63%), ethambutol (56%), and levofloxacin (12%). CONCLUSION: We analyzed ECMO's impact on drug concentrations and implemented therapeutic drug monitoring to optimize therapy. However, this single-case study has inherent limitations; future multi-center studies are warranted to validate these findings.
Effect of inhaled corticosteroid with oral montelukast and levocetirizine in asthma: A population-based study.
Park M, Woo SD, Park M … +2 more , Lee Y, Seo HJ
Int J Clin Pharmacol Ther · 2026 Apr · PMID 41502226 · Publisher ↗
INTRODUCTION: Asthma is a chronic disease that requires careful management, and its exacerbations can be life-threatening. The aim of this study was to ascertain whether inhaled corticosteroids (ICS)-containing inhaler i...
INTRODUCTION: Asthma is a chronic disease that requires careful management, and its exacerbations can be life-threatening. The aim of this study was to ascertain whether inhaled corticosteroids (ICS)-containing inhaler in combination with oral montelukast and levocetirizine could lessen the exacerbation of asthma in comparison to inhaler alone. MATERIALS AND METHODS: Among 437,915 asthma patients receiving ICS-containing inhaler, 91,122 participants were included. Treatment groups were categorized as (1) ICS-containing inhalers (ICS with or without long-acting β-2 agonist (LABA)), and (2) ICS-containing inhalers used in combination with both oral montelukast and levocetirizine, and (3) severe exacerbation of asthma (visit of emergency room or hospitalization). After 1 : 1 propensity score matching of treatment groups, survival analysis utilizing Cox regression was conducted for estimating the effect of treatment on asthma exacerbation. RESULTS: We found that the inhaler plus montelukast and levocetirizine group exhibited a lower crude incidence rate and was associated with a lower risk of all-cause death and moderate to severe exacerbation. Specifically, the adjusted hazard ratios (HRs) were 0.71 (p = 0.006) for all-cause death, 0.57 (p < 0.001) for moderate exacerbation. For severe exacerbations, the adjusted HRs were 0.59 for emergency room visits and 0.66 for hospitalizations (p = 0.018 and 0.011, respectively), compared to the ICS-only group, demonstrating a statistically significant reduction. CONCLUSION: Treatment with ICS-containing inhaler plus oral montelukast and levocetirizine was significantly associated with a lower risk of exacerbations in asthma patients. Alongside the growing burden of healthcare utilization and costs in South Korea, consideration of the treatment of ICS with montelukast and levocetirizine may serve as an effective treatment option for patients with severe, uncontrolled asthma, potentially improving disease management and reducing healthcare costs.
Parenteral replacement therapy with iron dextran or ferumoxytol in patients with iron deficiency.
Talamo G, Onishi R, Anand R … +5 more , Bekal S, Kuruvilla J, Khan M, Meseeha MG, Wurzler KL
Int J Clin Pharmacol Ther · 2026 Apr · PMID 41467635 · Publisher ↗
OBJECTIVE: To evaluate the changes in hematological parameters after replacement therapy with either iron dextran or ferumoxytol in patients with iron deficiency. MATERIALS AND METHODS: We conducted a retrospective revie...
OBJECTIVE: To evaluate the changes in hematological parameters after replacement therapy with either iron dextran or ferumoxytol in patients with iron deficiency. MATERIALS AND METHODS: We conducted a retrospective review of 246 consecutive patients with iron deficiency treated with a single intravenous (IV) infusion of a fixed dose of 1,025 mg of iron dextran (145 patients) or 1,020 mg of ferumoxytol (101 patients). Laboratory data were collected at baseline and at 2 - 3 months after replacement therapy. RESULTS: The median hemoglobin (Hb) and ferritin levels pre- and post-iron dextran were 9.5 (95% CI, 9.2 - 10.0) g/dL and 17 (95% CI, 14 - 20) ng/mL, and 12.0 (95% CI, 11.7 - 12.2) g/dL (p < 0.0001) and 123 (95% CI, 98 - 162) ng/mL (p < 0.0001), respectively. The median Hb and ferritin levels pre and post ferumoxytol were 10.4 (95% CI, 9.8 - 10.9) g/dL and 22 (95% CI, 18 - 28) ng/mL, and 12.5 (95% CI, 12.1 - 12.9) g/dL (p < 0.0001) and 129 (95% CI, 90 - 174) ng/mL (p < 0.0001), respectively. No statistically significant difference was observed between iron dextran and ferumoxytol in change of Hb levels, ferritin, transferrin saturation, mean corpuscular volume (MCV), and red cell distribution width (RDW). Transfusion reactions with iron dextran and ferumoxytol were observed in 2 (1.4%) and 3 (3%) patients, respectively (p = 0.65). CONCLUSION: In patients with iron deficiency, the change of the hematological parameters after replacement therapy was not statistically different between iron dextran and ferumoxytol. Our data suggests that these two formulations have similar efficacy and safety after the IV administration of equivalent doses.
Piperacillin/tazobactam-induced reversible pancytopenia in a pregnant patient: A case report.
He N, Wang S, Luo Q … +1 more , Yi W
Int J Clin Pharmacol Ther · 2026 Apr · PMID 41467634 · Publisher ↗
Hematologic responses (< 1%) to piperacillin/tazobactam were uncommon, and mostly reported in non-pregnant adults. The use of piperacillin/tazobactam during pregnancy is considered to be moderately safe for the human emb...
Hematologic responses (< 1%) to piperacillin/tazobactam were uncommon, and mostly reported in non-pregnant adults. The use of piperacillin/tazobactam during pregnancy is considered to be moderately safe for the human embryo-fetus (pregnancy grade B). However, changes in pharmacokinetics during pregnancy (such as an increase in plasma volume and an increase in renal clearance rate) may alter the toxicity threshold of the drug. This is a case of a pregnant woman (26 weeks of gestation) treated with piperacillin/tazobactam for psoas abscess (). After 22 days, the patient developed low-grade fever, leukopenia, neutropenia, and thrombocytopenia. Three days after discontinuation of piperacillin/tazobactam, the above adverse reactions were all reversed. The Naranjo scale yielded a score of 7, which indicates a definite result for this adverse drug reaction. This was the first report of piperacillin-tazobactam-induced pancytopenia in pregnancy.
The guanylate cyclase stimulator vericiguat: Insights and adverse events from a FAERS-based pharmacovigilance study.
Tang J, Lv B, Han J … +3 more , Li K, Li Q, Hu Y
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41467633 · Publisher ↗
BACKGROUND: Since its approval by the U.S. Food and Drug Administration in January 2021, vericiguat, a novel soluble guanylate cyclase stimulator, has been increasingly utilized in the treatment of heart failure with red...
BACKGROUND: Since its approval by the U.S. Food and Drug Administration in January 2021, vericiguat, a novel soluble guanylate cyclase stimulator, has been increasingly utilized in the treatment of heart failure with reduced ejection fraction. However, comprehensive long-term safety data on vericiguat in large populations are lacking. OBJECTIVE: This study analyzed the adverse events reported to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to assess the safety profile of vericiguat. MATERIALS AND METHODS: We selected four algorithms to evaluate the signals of adverse events related to vericiguat: Multi-item Gamma Poisson Shrinker, Bayesian Confidence Propagation Neural Network, Proportional Reporting Ratio, and Reporting Odds Ratio. RESULTS: We conducted a retrospective analysis of the FAERS database from January 19, 2021, to December 31, 2024, encompassing 6, 981, 085 reports. Among these, 1,863 adverse events from 886 reports were identified with vericiguat as the primary suspect. After applying all four algorithms at the preferred term level, 64 preferred terms were recognized, encompassing 853 signals. The most common adverse events, such as hypotension, dizziness, dyspepsia, and anemia, were consistent with findings of clinical trials. Additionally, we identified new adverse events, including gastrointestinal hemorrhage and renal impairment. CONCLUSION: Our analysis provides a comprehensive safety assessment of vericiguat. Most of these results align with findings from previous studies. In addition, our data revealed several new adverse events. This study provides valuable insights that can inform future research and clinical practice.
Semaglutide-induced transient intestinal ischemia: A case report.
Kalluru PKR, Cherukuri A, Kuchi D … +1 more , Topacio A
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41467632 · Publisher ↗
Obesity is a global health issue that impacts millions of people worldwide. Semaglutide is a glucagon-like peptide-1 receptor agonist that was initially developed as a treatment for type 2 diabetes mellitus under the bra...
Obesity is a global health issue that impacts millions of people worldwide. Semaglutide is a glucagon-like peptide-1 receptor agonist that was initially developed as a treatment for type 2 diabetes mellitus under the brand name Ozempic. Additional studies showed semaglutide at larger doses (marketed as Wegovy) to be an effective medication for weight management. Wegovy for managing obesity is typically well tolerated; however, there have been reports of gastrointestinal adverse effects. Only 1 case of Wegovy-induced transient intestinal ischemia has been documented, making it extremely unusual. Here, we report the case of a 50-year-old man who experienced transient intestinal ischemia following his first Wegovy dosage.
Dose optimization of linezolid among surgical patients: A population pharmacokinetic study.
Naseer MA, Aamir M, Bilal H … +3 more , Alsanie WF, Alamri AS, Usman M
Int J Clin Pharmacol Ther · 2026 Apr · PMID 41424326 · Publisher ↗
BACKGROUND: Linezolid is classified under the reserve group of antibiotics, and it exerts its antibacterial activity by disrupting protein synthesis. Clinically, linezolid is used for treatment of severe infections cause...
BACKGROUND: Linezolid is classified under the reserve group of antibiotics, and it exerts its antibacterial activity by disrupting protein synthesis. Clinically, linezolid is used for treatment of severe infections caused by methicillin-resistant (MRSA) and vancomycin-resistant (VRE). It is eliminated through both renal and hepatic routes. Being a narrow therapeutic index drug, linezolid needs special dosing considerations for safe and effective treatment. MATERIALS AND METHODS: A plasma concentration dataset of 94 patients with 347 samples was used for development of a population pharmacokinetic model on NONMEM software. The influence of significant covariates on pharmacokinetic parameters was analyzed by stepwise covariate modeling, and dosing simulations were performed on the basis of significant covariates. RESULTS: The data was best analyzed using a one-compartment model with first-order elimination. The clearance (CL) of linezolid was estimated as 3.38 L/h, while volume of distribution (Vd) was 36 L. The between-subject variability on linezolid CL was 29.8%, and that of Vd was 39.6%. Creatinine clearance (CrCl) and age of the patients were proven to be significant covariates on CL, while no significant covariate was observed for Vd during stepwise covariate modeling. The dosing simulations revealed that a different dose should be administered based on the CrCl of patients. CONCLUSION: The renal status and age of the patients are significant covariates responsible for linezolid CL, and a dose of 200, 300, 400, and 600 mg is appropriate for patients with CrCl of 20, 40, 80, and 120 mL/min, respectively.
Safety, pharmacokinetics, and pharmacodynamics of two regadenoson hyperaemic stress imaging injections in healthy Chinese subjects.
Liu Y, Wang CY, Wang HW … +7 more , Xu MQ, Zhang HW, Xie LJ, Chen J, Zhou C, Sun LN, Wang YQ
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41424325 · Publisher ↗
OBJECTIVE: This study evaluated and compared the safety, pharmacokinetics, and pharmacodynamics of regadenoson injection (test) and regadenoson original injection (Lexiscan, reference) in healthy Chinese subjects. MATERI...
OBJECTIVE: This study evaluated and compared the safety, pharmacokinetics, and pharmacodynamics of regadenoson injection (test) and regadenoson original injection (Lexiscan, reference) in healthy Chinese subjects. MATERIALS AND METHODS: In a randomized, positive-control, single-center, single-dose study, 24 healthy Chinese subjects were divided into test and reference groups (12 subjects each). Subjects in the test group received a single bolus of test drug (0.4 mg/5 mL), while the reference group received the same dose of reference drug. Blood and urine samples were collected before and after drug administration, and regadenoson concentrations were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: No serious adverse events (AEs) occurred. There was no significant difference in the incidence of adverse reactions between the two preparations. The pharmacokinetic parameters, including maximum concentration (C), the area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC), and the area under the concentration-time curve from time 0 to infinity (AUC), were assessed to compare the pharmacokinetic of two regadenoson preparations. The test/reference geometric mean ratios of C, AUC, and AUC were 102.84, 99.16, and 99.77%, respectively. The 90% confidence intervals (CIs) of AUC and AUC fell within 0.8 - 1.25, but the 90% CIs of C did not. Blood pressure (BP) and heart rate (HR) were measured to compare the pharmacodynamics of the two preparations. The test and reference drugs had similar HR responses (63.22 ± 38.45% vs. 37.50 ± 16.96%), systolic BP response (4.81 ± 13.73% vs. -3.83 ± 12.29%), and diastolic BP response (-7.75 ± 12.84% vs. -16.13 ± 9.85%), p > 0.05. After adjusting the weight of males and females, there were significant differences in C, AUC, AUC, T, V, λ, Ae%, p < 0.05. CONCLUSION: The test drug demonstrated similar pharmacokinetic and pharmacodynamic characteristics as the reference drug. Additionally, it was well-tolerated and safe in healthy Chinese participants. Sex may influence regadenoson pharmacokinetics.
Cardiotoxicity associated with antifungal agents: A pharmacovigilance analysis of the FDA Adverse Event Reporting System.
Cao D, Wei C, Yuan Y … +1 more , Wu B
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41378851 · Publisher ↗
OBJECTIVE: The aim of this study was to analyze the cardiotoxicity associated with antifungal agents based on data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). MATERIALS AND METHODS:...
OBJECTIVE: The aim of this study was to analyze the cardiotoxicity associated with antifungal agents based on data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS). MATERIALS AND METHODS: We extracted and evaluated cardiac adverse events (CAEs) linked to antifungals in the FAERS database (2004 - 2023). Signal strength for five antifungal classes was assessed using the reporting odds ratio (ROR) and information component (IC). RESULTS: Among 50,603 cases, triazoles, polyenes, and imidazoles showed significant associations with Torsade de Pointes (TdP)/QT prolongation (QTP), with fluconazole exhibiting the strongest link (ROR: 11.96, 95% CI: 10.62 - 13.46; IC: 2.19, 95% CI: 1.92 - 2.44). Triazoles were notably connected to arrhythmias, particularly itraconazole (ROR: 3.31, 95% CI: 2.88 - 3.79; IC: 1.67, 95% CI: 1.20 - 2.11). Fluconazole also demonstrated strong associations with conduction defects (ROR 6.44, 95% CI 5.60 - 7.39; IC 2.65, 95% CI 2.16 - 3.08) and ventricular tachyarrhythmias (ROR 9.09, 95% CI 7.84 - 10.54; IC 3.15, 95% CI 2.60 - 3.58). Notably, only itraconazole showed significant signals for cardiac failure (ROR 4.04, 95% CI 3.52 - 4.64; IC 1.96, 95% CI 1.48 - 2.40) and cardiomyopathy (ROR 6.34, 95% CI 5.04 - 7.96; IC 2.64, 95% CI 1.79 - 3.30). In contrast, echinocandins did not exhibit significant CAE signals. CONCLUSION: These findings highlight that azoles and polyenes show substantial associations with CAEs, particularly for TdP/QTP and arrhythmias. Itraconazole showed a significant association with cardiac failure and cardiomyopathy, while the signal for isavuconazole was weaker than for other triazoles. No significant cardiotoxicity signals were detected for echinocandins.
Prediction of anti-epileptic drug response of patients based on peripheral blood RNA profiles and machine learning.
Liu ZD, Kou ZY, Guo L
Int J Clin Pharmacol Ther · 2026 Feb · PMID 41378850 · Publisher ↗
OBJECTIVE: In this study, we aimed to develop a method for predicting the response of patients to three commonly used anti-epileptic drugs (AEDs), namely, carbamazepine, phenytoin, and valproate, using machine learning m...
OBJECTIVE: In this study, we aimed to develop a method for predicting the response of patients to three commonly used anti-epileptic drugs (AEDs), namely, carbamazepine, phenytoin, and valproate, using machine learning models, based on the patients' peripheral blood RNA profiles. MATERIALS AND METHODS: A data set from the Gene Expression Omnibus Series database (GSE143272) was utilized that included the peripheral blood RNA information and some clinical features (age, weight, sex, epilepsy type, drug response) of 57 epilepsy patients. 22 classification models were constructed and trained, in which the peripheral blood RNA information, age, weight, sex, and epilepsy type served as predictors, and the patient' response to anti-epileptic drug as the outcome. The predicting capacity was evaluated by utilizing the sensitivity, the specificity, and the receiver operating characteristic curve of the models. RESULTS: Among the 22 trained models, the model of a quadratic support vector machine with a pretreatment of principal component analysis displayed the highest accuracy at 0.75, and the highest value of area under ROC curve at 0.81. CONCLUSION: The model of a quadratic support vector machine with a pretreatment of principal component analysis is a potential tool for predicting the response of patients with epilepsy to drug treatment.
Determination of antimicrobial resistance pattern among post-operative orthopedic implant patients in a tertiary care hospital: A retrospective study.
Nazeer H, Khan HM, Hannan MA … +6 more , Zulfiqar S, Gul B, Alhomrani M, Alamri AS, Alsanie WF, Usman M
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41378849 · Publisher ↗
BACKGROUND: The misuse of antibiotics leads to antimicrobial resistance, particularly concerning infections related to orthopedic implants. The aim of this study was to determine the sensitivity pattern of bacterial isol...
BACKGROUND: The misuse of antibiotics leads to antimicrobial resistance, particularly concerning infections related to orthopedic implants. The aim of this study was to determine the sensitivity pattern of bacterial isolates in patients with orthopedic implants having infections. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted at Ghurki Trust Teaching Hospital, Lahore. Culture sensitivity reports from 548 patients were collected between January 2020 and March 2023. Patient demographics, including age, sex, culture specimens (blood, wound, etc.), and antibiotic sensitivity were recorded. RESULTS: Seven types of implants were analyzed, with Ilizarov (25.5%) being the most infected external implant and nails (24.7%) the most infected internal implant. The study included 10 clinically significant bacteria, with (n = 195, 35.5%) being the most common Gram-positive pathogen, and (n = 99, 18.0%) being the most prevalent Gram-negative pathogen. A total of 40 antibiotics were tested; amoxicillin was the least effective, whereas linezolid, vancomycin, and fosfomycin showed the highest efficacy against all implant-related infections included in this study. CONCLUSION: The critical challenges of antimicrobial resistance in orthopedic implant-related infections have been highlighted. Urgent institutional and policy level interventions are required for implementation of stringent infection control protocols and robust antibiotic stewardship programs to prevent a post-antibiotic crisis.
Population pharmacokinetics of tofacitinib in patients with active ankylosing spondylitis.
Tsuchiwata S, Suzuki A, Wang Q … +3 more , Kanik K, Fallon L, Menon S
Int J Clin Pharmacol Ther · 2026 Feb · PMID 41355395 · Full text
OBJECTIVE: To characterize tofacitinib pharmacokinetics (PK) in patients with active ankylosing spondylitis (AS) and estimate the effects of covariates on variability of PK parameters. MATERIALS AND METHODS: Pooled data...
OBJECTIVE: To characterize tofacitinib pharmacokinetics (PK) in patients with active ankylosing spondylitis (AS) and estimate the effects of covariates on variability of PK parameters. MATERIALS AND METHODS: Pooled data from two studies in patients with AS who received tofacitinib were analyzed using nonlinear mixed-effects modeling. Tofacitinib PK was described by a one-compartment model parameterized in terms of apparent oral clearance (CL/F), apparent volume of distribution (V/F), and a first-order absorption rate constant (k). Covariates evaluated: baseline age, sex, race, creatinine clearance (BCCL), and C-reactive protein for CL/F; baseline age/body weight for V/F. RESULTS: Analysis included 279 patients. The point estimates for CL/F, V/F, and k were 27.1 L/hour, 126 L, and 3.07 hour, respectively, in a reference patient. Excluding BCCL, point estimates of area under the concentration-time curve (AUC) over a dosing interval at steady-state and maximum steady-state tofacitinib concentration (C) change vs. the reference patient ranged from 98 - 112% and 89 - 115%, respectively. Estimated AUC was 24% higher in a patient with BCCL = 50 mL/min vs. the reference patient (BCCL = 126 mL/min). Point estimates and 90% confidence intervals of the AUC and C ratios indicated no major differences in tofacitinib exposure over the range of baseline age/body weight studied, and sex/race. CONCLUSION: Tofacitinib does not require dose adjustment/restriction for age, body weight, sex, or race based on the differences (< 20%) in exposure relative to a reference patient with AS. The tofacitinib CL/F and BCCL relationship was consistent with known contribution of renal excretion to total tofacitinib clearance.
Comparison of vasopressin-first weaning versus norepinephrine-first weaning in critically ill patients.
Alshreef M, AbaAlkhayl H, Almdainy Q … +6 more , Alshammari A, Alajmi S, Alruwaite S, Alqahtani E, Almalke R, Alonazi T
Int J Clin Pharmacol Ther · 2026 Feb · PMID 41347381 · Full text
BACKGROUND: Septic shock is a critical condition requiring vasopressor support and mechanical ventilation. The sequence of vasopressor weaning may affect clinical outcomes, such as mechanical ventilation duration and pat...
BACKGROUND: Septic shock is a critical condition requiring vasopressor support and mechanical ventilation. The sequence of vasopressor weaning may affect clinical outcomes, such as mechanical ventilation duration and patient survival. OBJECTIVES: This study assesses how vasopressor weaning order affects hemodynamic stability, clinical outcomes, and the length of mechanical ventilation in critically ill septic shock patients. MATERIALS AND METHODS: A retrospective cohort study was conducted at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, from January 2022 to December 2023. Critically ill adult patients receiving intravenous norepinephrine and vasopressin for septic shock and requiring mechanical ventilation were included. Patients were classified into two groups: vasopressin weaned first or norepinephrine weaned first. The duration of mechanical ventilation was the main outcome. These were secondary outcomes: mean arterial pressure (MAP) stability, 30-day and in-hospital mortality, length of stay (LOS) in the intensive care unit and hospital, and rates of reintubation. RESULTS: Among 100 patients (mean age: 65.1 ± 19.7 years; 58% male), vasopressin was weaned first in 47 patients (47%) and norepinephrine first in 53 (53%). Patients extubated while on vasopressors (vasopressin weaned first) had a shorter median duration of mechanical ventilation (4 days) and lower odds of mortality (adjusted OR = 0.30, 95% CI: 0.09 - 0.98; p = 0.046) compared to those weaned off norepinephrine first. No significant differences were observed in reintubation rates or LOS. CONCLUSION: Weaning vasopressin before norepinephrine may be associated with improved survival and reduced mechanical ventilation duration in septic shock patients, although further research is needed to validate these findings and optimize vasopressor weaning strategies.
Adverse reactions of PD-1/PD-L1 inhibitors in cancer: FAERS database analysis and protocols to mitigate immune-related events in elderly patients and when using pembrolizumab and atezolizumab.
He S, Chen J, Gu L … +3 more , Zeng W, Li T, Zhao W
Int J Clin Pharmacol Ther · 2026 Mar · PMID 41347380 · Publisher ↗
OBJECTIVE: This study aimed to characterize adverse drug reactions (ADRs) associated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in cancer immunotherapy, identifying demographic, pharmacolog...
OBJECTIVE: This study aimed to characterize adverse drug reactions (ADRs) associated with programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in cancer immunotherapy, identifying demographic, pharmacological, and clinical determinants of toxicity severity using real-world pharmacovigilance data. MATERIALS AND METHODS: We analyzed 93,925 ADR reports from the FDA Adverse Event Reporting System (FAERS, 2023-2024). Data preprocessing included deduplication, terminology standardization, and severity classification. Multivariate logistic regression and machine learning models were employed to assess predictors of serious ADRs, integrating demographic variables (age, sex), drug agents, and organ-specific toxicities. RESULTS: Pembrolizumab (38.4%), atezolizumab (26.5%), and nivolumab (25.0%) accounted for 89.9% of ADR cases. Frequent ADRs included death (7.9%), off-label use (7.5%), and malignant progression (6.9%). Immune-related toxicities (diarrhea, hypothyroidism, pneumonitis) comprised 6.1 - 2.4% of cases. Severe ADRs (grade 3 - 4) predominantly affected hepatic (68%), cardiac (65%), and neurological systems (62%). Octogenarians exhibited a 42% increased risk of serious ADRs (p < 0.001), with males representing 51.1% of severe cases (p < 0.001). CONCLUSION: Age, sex, and drug-specific profiles critically influence PD-1/PD-L1 inhibitor toxicity. The findings support personalized risk stratification and time-dependent monitoring protocols to mitigate immune-related adverse events, particularly in elderly and male patients. These insights enhance evidence-based management strategies for optimizing immunotherapy safety.
Effect of extracorporeal anticoagulation with nafamostat mesilate and continuous renal replacement therapy in sepsis complicated by acute kidney injury.
Zhang J, Shao H, Zhu D … +2 more , Zhang G, He Y
Int J Clin Pharmacol Ther · 2026 Feb · PMID 41347379 · Publisher ↗
OBJECTIVE: We aimed to evaluate the effect of extracorporeal anticoagulation with nafamostat mesilate (NM) and continuous renal replacement therapy (CRRT) on sepsis complicated with acute kidney injury (AKI). MATERIALS A...
OBJECTIVE: We aimed to evaluate the effect of extracorporeal anticoagulation with nafamostat mesilate (NM) and continuous renal replacement therapy (CRRT) on sepsis complicated with acute kidney injury (AKI). MATERIALS AND METHODS: The clinical data of 106 sepsis patients complicated with AKI admitted from January 2023 to December 2024 were retrospectively analyzed. According to different treatment protocols, the patients were assigned into a control group (n = 53, regional citrate anticoagulation (RCA) plus CRRT) and a study group (n = 53, NM extracorporeal anticoagulation plus CRRT). The use of extracorporeal circulation circuit was compared. RESULTS: After 3 days of treatment, the levels of procalcitonin, interleukin-6, and tumor necrosis factor-α decreased in the two groups compared to those before treatment (p < 0.05), and they were lower in the study group than in the control group (p < 0.05). After 3 days of treatment, both groups had lowered levels of serum creatinine (Scr), cystatin C (Cys-C), and blood urea nitrogen (BUN), together with increased mean transit time (MTT), peak intensity (PI), and area under the curve (AUC) compared with those before treatment. In the study group, the levels of Scr, Cys-C, and BUN declined, while MTT, PI, and AUC rose compared with those in the control group (p < 0.05). The incidence of adverse reactions in the study group was lower than that in the control group (3.77 vs. 16.98%) (p < 0.05). CONCLUSION: NM outperforms RCA in prolonging the hemofilter lifespan, reducing hemofilter replacement frequency, improving renal perfusion and renal function, and eliminating inflammatory mediators.
Pegylated liposomal doxorubicin-induced hand-foot syndrome in a patient with breast cancer: Case report and FAERS database analysis.
Qu K, Zhao J, Zhang Y … +1 more , Li J
Int J Clin Pharmacol Ther · 2026 Jan · PMID 41190421 · Publisher ↗
Hand-foot syndrome (HFS) is a relatively common, dose-limiting dermatologic toxic reaction associated with multiple chemotherapeutic agents, including pegylated liposomal doxorubicin (PLD). Early symptoms of HFS include...
Hand-foot syndrome (HFS) is a relatively common, dose-limiting dermatologic toxic reaction associated with multiple chemotherapeutic agents, including pegylated liposomal doxorubicin (PLD). Early symptoms of HFS include erythema, marked discomfort, swelling, and tingling on the palms and soles of the feet, which may progress to blistering and even ulceration in severe cases. We report a case of a breast cancer patient who developed HFS after receiving 3 cycles of PLD. The patient presented with redness, swelling, blistering, ulceration, and exudation in her palms, soles, axillae, groin, and waist. After symptomatic treatment, her HFS symptoms were significantly relieved. At the same time, we have also examined the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data for further reports of the relationship between different anthracyclines and risk of HFS.
Medical diagnostic acumen and artificial intelligence.
Woodcock-Kloberdanz BG
Int J Clin Pharmacol Ther · 2025 Dec · PMID 41165225 · Publisher ↗
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Entecavir HPLC-MS/MS quantitation and optimized sample preparation using human plasma: Validation in a pharmacokinetic study.
Zhao R, Li P, Liu H … +2 more , Du P, Liu L
Int J Clin Pharmacol Ther · 2026 Feb · PMID 41147151 · Publisher ↗
AIMS: To determine the entecavir levels in human plasma using a quantitative high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technique. MATERIALS AND METHODS: The developed method employed is...
AIMS: To determine the entecavir levels in human plasma using a quantitative high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technique. MATERIALS AND METHODS: The developed method employed isotope-labeled internal standard, a high-throughput solid phase extraction process for sample preparation, and HPLC-MS/MS analysis using multiple reaction monitoring transitions in positive mode. RESULTS: With a 0.025 - 10 ng/mL linear range, interday and intraday accuracy ranged from -3.4 to 5.3%; between-day and within-day precision was ≤ 7.3%. Stability, matrix effect, and recovery were all well within the acceptable criteria. A pharmacokinetic study of entecavir dispersible tablets at an oral dosage of 0.5 mg was successfully carried out using the validated method. CONCLUSION: The established HPLC-MS/MS method proved effective for quantitation of entecavir in human plasma.
Analysis of the clinical characteristics and risk factors for dabigatran-induced bleeding in patients with nonvalvular atrial fibrillation.
Wang X, Wang X, Li Y … +2 more , Yang Z, Wu D
Int J Clin Pharmacol Ther · 2026 Jan · PMID 41122012 · Publisher ↗
OBJECTIVE: To explore the clinical characteristics of dabigatran-induced bleeding and analyze its risk factors in patients with nonvalvular atrial fibrillation (NVAF). MATERIALS AND METHODS: A retrospective analysis was...
OBJECTIVE: To explore the clinical characteristics of dabigatran-induced bleeding and analyze its risk factors in patients with nonvalvular atrial fibrillation (NVAF). MATERIALS AND METHODS: A retrospective analysis was conducted on patients with NVAF who received 110 mg of dabigatran twice daily from January 2020 to March 2023. Patients were divided into a long-term-use group and a first-time-use group on the basis of their duration of medication use. The impact of long-term dabigatran use on coagulation function was analyzed. Furthermore, patients in the long-term-use group were divided into bleeding and nonbleeding subgroups. Multivariate logistic regression analysis was used to determine the risk factors for bleeding. Clinical data such as underlying diseases, concomitant medications, bleeding types, and bleeding sites were collected. RESULTS: A total of 531 cases were collected, including 214 in the long-term-use group and 317 in the first-time-use group. In addition to fibrinogen (p > 0.05), coagulation function indicators, including the prothrombin time, prothrombin time percentage, international normalized ratio, activated partial thromboplastin time, and thrombin time (TT), were greater in the long-term-use group than in the first-time-use group, whereas D-dimer values were significantly lower in the long-term-use group (p < 0.05). A total of 63 bleeding cases were found, with an overall bleeding rate of 11.86%. The bleeding type was BARC type 1 (87.30%), and the bleeding site was mainly gastrointestinal bleeding (77.78%). Multivariate logistic regression analysis revealed that a TT value > 116 s (OR 0.385, 95% CI 0.150 - 0.984; p = 0.038) and the presence of heart failure (OR 0.341, 95% CI 0.133 - 0.875; p = 0.025) were risk factors for bleeding in patients on long-term dabigatran therapy. CONCLUSION: The probability of bleeding caused by long-term use of dabigatran is relatively high, but it is mainly minor bleeding. The long-term use of dabigatran has an impact on multiple coagulation function indicators. Clinical physicians and pharmacists need to closely monitor patients' TT values and whether they have heart failure and identify high-risk populations for bleeding as early as possible.
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