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Background and Aim: The association between proton‐pump inhibitors (PPIs) and rhabdomyolysis were unclear. The aim of this study was to explore and systematically analyze the potential link between five PPIs and the rhabdomyolysis events using the FDA Adverse Event Reporting System (FAERS) database. Methods: Suspected rhabdomyolysis events associated with PPIs were identified by data mining with the reporting odds ratio (ROR), proportional reporting ratio (PRR), the information component (IC), and Empirical Bayes Geometric Mean (EBGM). Demographic information, drug administration, and outcomes of PPI‐induced rhabdomyolysis events were also analyzed. Results: There were 3311 reports associated with PPI‐induced rhabdomyolysis that were identified. After removing duplicates, 1899 cases were determined to contain complete patient demographic data. The average age was 65 ± 18 year and 57% were male. Omeprazole and pantoprazole had the same largest percentage of reports. Lansoprazole had the highest ROR index of 12.67, followed by esomeprazole (11.18), omeprazole (10.27), rabeprazole (10.06), and pantoprazole (9.24). PRR, IC, and EBGM showed similar patterns. This suggested that lansoprazole exhibited the strongest correlation with rhabdomyolysis. In rhabdomyolysis events, PPIs were mainly "concomitant" (>60%), and only a few cases were "primary suspects" (<15%). Rabeprazole showed the lowest death rate while lansoprazole showed the highest. Conclusions: The study suggested that significant rhabdomyolysis signals were associated with PPIs. Further research should be performed in drug safety evaluation for a more comprehensive association. [ABSTRACT FROM AUTHOR]

Tacrolimus was frequently used in pediatric patients with umbilical cord blood transplant for the prevention of graft‐versus‐host disease. The aim of the present study was to evaluate the population pharmacokinetics of tacrolimus among pediatric patients with umbilical cord blood transplant and find potential influenced factors. A total of 275 concentrations from 13 pediatric patients were used to build a polulation pharmacokinetic model using a nonlinear mixed‐effects modeling approach. The impact of demographic features, biological characteristics, and concomitant medications, including sex, age, body weight, postoperative day, white blood cell count, red blood cell count, hemoglobin, platelets, hematocrit, blood urea nitrogen, creatinine, aspartate transaminase, alanine transaminase, total bilirubin, albumin, and total protein were investigated. The pharmacokinetics of tacrolimus were best described by a 1‐compartment model with first‐ and zero‐order mixed absorption and first‐order elimination. The clearance and volume of distribution of tacrolimus were 1.93 L/h and 75.1 L, respectively. A covariate analysis identified that postoperative day and co‑administration with trimethoprim‐sulfamethoxazole were significant covariates influencing clearance of tacrolimus. Frequent blood monitoring and dose adjustment might be needed with the prolongation of postoperative day and coadministration with trimethoprim‐sulfamethoxazole. [ABSTRACT FROM AUTHOR]

What is known and objective: Linezolid is an alternative first‐line agent for MRSA pneumonia. This study assessed whether dose adjustments of linezolid against methicillin‐resistant Staphylococcus aureus (MRSA) infections were needed based on renal function in populations with different body weight. Methods: Monte Carlo simulations were conducted to evaluate renal function in relation to the probability of target attainment (PTA) in three population groups with different body weight. Area under the concentration time curve (AUC)/ minimum inhibitory concentration (MIC) ratio and percentage of time above the MIC (%T > MIC) were regarded as pharmacokinetic/pharmacodynamic targets. The PTA and cumulative fractions of response (CFR) were calculated to assess the efficacy. Regarding safety, trough plasma concentration (Cmin) > 8 mg/L was used as target for toxicity. Results and discussion: Using AUC/MIC >100 as the target pharmacodynamic (PD) index, the CFR of linezolid at the standard dose (600 mg every 12 h [q12h]) were 57.01%, 93.22%, and 99.93% in patients with normal renal function, patients with renal dysfunction and low body weight patients with renal dysfunction, respectively. Using 100%T > MIC as the target PD index, all the CFR of three population groups were more than 90% at the standard dose. The percentages of Cmin > 8 mg/L at the standard dose of linezolid were 24.16%, 53.24%, and 90.10% in three population groups on day 7. What is new and conclusion: The risk of thrombocytopenia of linezolid was extremely higher in low body weight patients with renal impairment when receiving standard linezolid dose compared with patients with normal renal function. 450 mg q12h and 300 mg q12h might be effective and safe against MRSA infection in patients with renal dysfunction and low body weight patients with renal dysfunction, respectively. [ABSTRACT FROM AUTHOR]