Wiley: Clinical Pharmacology in Drug Development: Table of Contents

Population Pharmacokinetic‐Based Meropenem Dosing in Critically and Non‐Critically Ill Patients with Mixed Gram‐Negative Bacterial Infections

Shuo Shi, Jie Cui, Guangqing Liu, Jin Gao, Wanjun Bai — Thu, 04 Jun 2026 20:40:36 -0700

Abstract

This study aimed to describe the population pharmacokinetic (PK) of meropenem in patients with mixed Gram-negative bacterial infections, and further to develop optimal dosing regimens for both non-critically ill and critically ill patients by combining different pharmacokinetic/pharmacodynamic (PK/PD) targets. Based on retrospectively collected data from patients who underwent therapeutic drug monitoring (TDM) for meropenem, including demographic characteristics, medication records, and laboratory results, a population PK model was developed via nonlinear mixed-effects modeling. Dosing regimens were subsequently evaluated and provided through Monte Carlo simulation. The population PK analysis of meropenem included 86 steady-state concentrations from 39 adult patients. The data were modeled using a one-compartment model. The final model yielded a population typical value for clearance (CL) of 6.10 L/h. Our study showed that estimated glomerular filtration rate (eGFR) significantly affected the PK of meropenem. Monte Carlo simulation results demonstrated that a regimen of 0.5-h infusion every 8 h was sufficient to achieve the conventional target of 40% ƒT > MIC in most scenarios. In contrast, achieving the more aggressive target of 100% ƒT > MIC required a regimen of every 6 h; for MIC ≥ 4 mg/L pathogens, this needed to be coupled with an extended infusion time of 3 h. Furthermore, continuous infusion regimens demonstrated a distinct advantage in critically ill patients. This study successfully established a population PK model of meropenem and provided a reference for dosing adjustment based on clinical severity and renal function.

Effect of High‐Fat Meal on the Pharmacokinetics and Safety of Lansoprazole Enteric‐Coated Capsules in Healthy Chinese Subjects

Thu, 04 Jun 2026 02:09:42 -0700

Abstract

The effects of food on the pharmacokinetics (PKs) and safety of 30-mg lansoprazole enteric-coated capsules in healthy Chinese subjects were investigated from a bioequivalence trial. A randomized, open-label, four-period crossover study was conducted in 73 healthy subjects under both fasted and fed conditions. Serial blood samples were collected, and plasma lansoprazole concentrations were determined by liquid chromatography-tandem mass spectrometry. PK parameters were calculated using a non-compartmental model with Phoenix WinNonlin Version 8.3 software. The bioequivalence module of WinNonLin was used to statistically analyze the maximum plasma concentration (C_max), the area under the concentration–time curve from zero to the last measurable concentration (AUC_0-t), and the area under the concentration–time curve from zero to infinity (AUC_0-∞) of lansoprazole in plasma. The results demonstrated bioequivalence between the test (T) and reference (R) formulations for all evaluated PK parameters. Compared with the fasted state, the C_max, AUC_0-t, and AUC_0-∞ of lansoprazole significantly decreased by 60.67%, 46.39%, and 44.25%, respectively, following oral administration of lansoprazole 30 mg in the fed state. The incidence of adverse events (AEs) was similar between the fasted and fed states, with no serious AEs observed. Overall, food markedly reduced systemic exposure of 30 mg oral lansoprazole in Chinese subjects, indicating that food intake significantly affects its bioavailability.

Scientific Fraud: How Do We Ensure Sound Medical Literature?

Michael J. Fossler, Katy P. Moore — Mon, 01 Jun 2026 07:18:57 -0700

Clinical Pharmacology in Drug Development, Volume 15, Issue 6, June 2026.

Pacritinib Impact on QT Interval: Results of a Thorough QT Study and Post Hoc Analysis of Prospective Clinical Trial Data

Fri, 29 May 2026 08:50:03 -0700

Abstract

Pacritinib, an inhibitor of JAK2/IRAK1/ACVR1 that is devoid of JAK1 activity, approved for treating myelofibrosis in patients with severe thrombocytopenia, carries a label warning for QT interval prolongation. To evaluate the cardiac safety of pacritinib, a randomized, placebo- and active-controlled, single-dose thorough QT (TQT) study was conducted in healthy subjects, and a dose-finding study (PAC203) was conducted in patients with myelofibrosis. In the TQT study, 42 subjects received single doses of pacritinib 400 mg, moxifloxacin 400 mg (positive control), and placebo in a crossover design. The maximal placebo-corrected change in QT interval with pacritinib was −9.7 ms (90% confidence interval: −13.4, −6.1), and all upper confidence bounds were <10 ms. A small, clinically irrelevant inverse concentration–QTc relationship was observed. No subject administered pacritinib had a QTc interval using Fridericia's formula (QTcF) >480 ms or a change from baseline in QTcF >30 ms. Moreover, in the PAC203 trial, there was no correlation between pacritinib exposure and QTcF at weeks 12 or 24. Median QTcF changes from pre-dose to 4 h post-dose were minimal (+2.7 and −0.3 ms, respectively), and no dose–response relationship was identified. These findings suggest that pacritinib exposure is unlikely to be correlated with QT prolongation.

Pharmacokinetics and Tolerability of Entacapone, Levodopa, and Carbidopa Tablets in Healthy Chinese Subjects: A Randomized, Open‐Label, Four‐Period Crossover Study Under Fasting and Fed Conditions

Jingyan Wang, Yuan Xu, Ye Tao, Xuewei Ma, Yang Zou, Zhen Yang, Yi Lan — Fri, 29 May 2026 03:44:43 -0700

Abstract

This study aimed to assess the pharmacokinetics, bioequivalence, and safety of a generic entacapone/levodopa/carbidopa (100/25/200 mg) tablet formulation compared to its reference listed drug (RLD, Stalevo) in healthy Chinese adults. A randomized, open-label, single-dose, four-period crossover study was conducted under fasting and fed conditions, with a 5-day washout. A total of 68 subjects were enrolled and randomly assigned (1:1) to receive a single oral dose of either the test or reference formulation. Plasma concentrations of analytes were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and key pharmacokinetic parameters (C_max, AUC_0–t, AUC_0–∞) were calculated. Under both fasting and fed conditions, bioequivalence was assessed under both fasting and fed conditions using the reference-scaled average bioequivalence (RSABE) or average bioequivalence (ABE) approach. For the key pharmacokinetic parameters (C_max, AUC_0–t, and AUC_0–∞), the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) all fell within the 80.00%–125.00% range, or the one-sided 95% upper confidence bound for the scaled difference was ≤0 and the point estimate of the GMR between the test and reference formulations fell within the 80.00%–125.00% range, thus confirming bioequivalence. Concomitant high-fat food intake had a certain impact on the pharmacokinetics of each active ingredient. Adverse events (AEs) were mild, with no serious AEs reported, indicating comparable safety profiles. In conclusion, the generic formulation is bioequivalent to the RLD and demonstrates an acceptable safety profile in healthy Chinese subjects.

Comparative Pharmacokinetics of Two Extended‐Release Tablet Formulations of Upadacitinib: Bioequivalence Assessment

Biao Sun, Li Zhao, Fangliang Gan, Qiong Zhan — Fri, 29 May 2026 03:32:17 -0700

Abstract

The aim of this study is to evaluate the pharmacokinetic characteristics, bioequivalence, and safety of two brands of upadacitinib (UPA) extended-release tablets (15 mg) in healthy Chinese subjects under fasting and postprandial conditions. The plasma concentration of UPA was determined by ultra-high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were calculated using a non-compartmental model (NCA module) with Phoenix WinNonlin 8.2 (Certara, USA) software, followed by bioequivalence evaluation. The results demonstrate that the 90% confidence intervals for the geometric least-squares mean ratios of C_max, AUC_0–t, and AUC_0–∞ between the test and reference formulations fall within the range of 0.80−1.25, indicating that both formulations are bioequivalent in terms of absorption rate and extent under fasting and postprandial conditions. No serious adverse events occurred, and observed drug-related adverse events were mild under both conditions, indicating comparable safety of the two formulations.

Issue Information

Fri, 29 May 2026 03:30:55 -0700

Clinical Pharmacology in Drug Development, Volume 15, Issue 6, June 2026.