Pharmacokinetics of 2,000 Milligram Ertapenem in Tuberculosis Patients.

Autor: Zuur MA; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands., Ghimire S; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands., Bolhuis MS; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands., Wessels AMA; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands., van Altena R; University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands., de Lange WCM; University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands., Kosterink JGW; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.; University of Groningen, Groningen Research Institute of Pharmacy, PharmacoTherapy, Epidemiology and Economics, Groningen, The Netherlands., Touw DJ; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands.; University of Groningen, Groningen Research Institute of Pharmacy, Section Pharmacokinetics, Toxicology and Targeting, Groningen, The Netherlands., van der Werf TS; University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Department of Internal Medicine, Groningen, The Netherlands., Akkerman OW; University of Groningen, University Medical Center Groningen, Department of Pulmonary Diseases and Tuberculosis, Groningen, The Netherlands.; University of Groningen, University Medical Center Groningen, Tuberculosis Center Beatrixoord, Haren, The Netherlands., Alffenaar JWC; University of Groningen, University Medical Center Groningen, Department of Clinical Pharmacy and Pharmacology, Groningen, The Netherlands j.w.c.alffenaar@umcg.nl.
Jazyk: angličtina
Zdroj: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2018 Apr 26; Vol. 62 (5). Date of Electronic Publication: 2018 Apr 26 (Print Publication: 2018).
DOI: 10.1128/AAC.02250-17
Abstrakt: Ertapenem is a carbapenem antibiotic with activity against Mycobacterium tuberculosis Dose simulations in a hollow-fiber infection model showed that 2,000 mg once daily is an appropriate dose to be tested in clinical studies. Before using this dose in a phase II study, the aim of this prospective pharmacokinetic study was to confirm the pharmacokinetics of 2,000 mg once daily in tuberculosis (TB) patients. Twelve TB patients received a single intravenous dose of 2,000 mg ertapenem as a 30-min infusion. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 8, 12, and 24 h postadministration. Drug concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay. A large interindividual variation in the pharmacokinetics of ertapenem was observed. The median (interquartile range) area under the plasma concentration-time curve to infinity (AUC 0-∞ ) was 2,032 (1,751 to 2,346) mg · h/liter, the intercompartmental clearance (CL 12 ) was 1.941 (0.979 to 2.817) liters/h, and the volume of distribution in the central compartment ( V 1 ) was 1.514 (1.064 to 2.210) liters. A more than dose-proportional increase in AUC was observed compared to results reported for 1,000 mg ertapenem in multidrug-resistant TB patients. Based on a MIC of 1.0 mg/liter, 11 out of 12 patients would have reached the target value of unbound drug exceeding the MIC over 40% of the time ( f 40% T >MIC). In conclusion, this study shows that 2,000 mg ertapenem once daily in TB patients reached the expected f 40% T >MIC for most of the patients, and exploration in a phase 2 study can be advocated.
(Copyright © 2018 American Society for Microbiology.)
Databáze: MEDLINE
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