Details

Autor(en) / Beteiligte

• Zuur, M A
• Ghimire, S
• Bolhuis, M S
• Wessels, A M A
• van Altena, R
• de Lange, W C M
• Kosterink, J G W
• Touw, D J
• van der Werf, T S
• Akkerman, O W
• Alffenaar, J W C

Titel

Pharmacokinetics of 2,000 Milligram Ertapenem in Tuberculosis Patients

Ist Teil von

• Antimicrobial agents and chemotherapy, 2018-05, Vol.62 (5)

Ort / Verlag

United States: American Society for Microbiology

Erscheinungsjahr

2018

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Ertapenem is a carbapenem antibiotic with activity against 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 ) was 2,032 (1,751 to 2,346) mg · h/liter, the intercompartmental clearance (CL ) was 1.941 (0.979 to 2.817) liters/h, and the volume of distribution in the central compartment ( ) 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 ( 40% >MIC). In conclusion, this study shows that 2,000 mg ertapenem once daily in TB patients reached the expected 40% >MIC for most of the patients, and exploration in a phase 2 study can be advocated.