The Population Pharmacokinetics of Meropenem in Adult Patients With Rifampicin-Sensitive Pulmonary Tuberculosis

• DOI: 10.3389/fphar.2021.637618
• Publication Date: 2021-06-29T04:56:37Z
• Authors: Ahmed A. Abulfathi; Veronique de Jager; Elana van Brakel; Helmuth Reuter; Nikhil Gupte; Naadira Vanker; Grace L. Barnes; Eric Nuermberger; Susan E. Dorman; Andreas H. Diacon; Kelly E. Dooley; Elin M. Svensson
• Keywords: NONMEM

Background: Meropenem is being investigated for repurposing as an anti-tuberculosis drug. This study aimed to develop a meropenem population pharmacokinetics model in patients with pulmonary tuberculosis and identify covariates explaining inter-individual variability. Methods: Patients were randomized one of four treatment groups: 2 g three times daily plus oral rifampicin 20 mg/kg once daily, 1 3 daily. was administered by intravenous infusion over 0.5-1 h. All also received amoxicillin/clavulanate together each dose, treatments continued 14 days. Intensive plasma sampling 8 h conducted on the 14th day study. Nonlinear mixed-effects modeling used data analysis. The best chosen based likelihood metrics, goodness-of-fit plots, parsimony. Covariates tested stepwise. Results: A total 404 concentration measurements from 49 included two-compartment parameterized clearance (CL), inter-compartmental (Q), central (V1) peripheral (V2) volumes distribution fitted well. Typical values CL, Q, V1, V2 11.8 L/h, 3.26 14.2 L, 3.12 respectively. relative standard errors parameter estimates ranged 3.8 35.4%. covariate relations final creatinine CL allometric scaling body weight all disposition parameters. An effect age previously reported could not be identified. Conclusion: described found improve fit but treatment. will integrated pharmacokinetics/pharmacodynamics analysis linking exposure early bactericidal activity.