Pharmacokinetics of extended-release clarithromycin in patients with Mycobacterium ulcerans infection.

Autor: Klis SA; Department of Internal Medicine-Infectious Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands., Stienstra Y; Department of Internal Medicine-Infectious Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK., Abass KM; Agogo Presbyterian Hospital, Agogo, Ghana., Abottsi J; Agogo Presbyterian Hospital, Agogo, Ghana., Mireku SO; Agogo Presbyterian Hospital, Agogo, Ghana., Alffenaar JW; The University of Sydney Institute for Infectious Diseases, Sydney, NSW, Australia.; Faculty of Medicine and Health, School of Pharmacy, The University of Sydney, Sydney, NSW, Australia.; Westmead Hospital, Sydney, NSW, Australia., van der Werf TS; Department of Internal Medicine-Infectious Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. t.s.van.der.werf@umcg.nl.; Department of Pulmonary Diseases & Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. t.s.van.der.werf@umcg.nl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Aug 28; Vol. 14 (1), pp. 19963. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1038/s41598-024-70890-w
Abstrakt: Clarithromycin extended-release (CLA-ER) was used as companion drug to rifampicin (RIF) for Mycobacterium ulcerans infection in the intervention arm of a WHO drug trial. RIF enhances CYP3A4 metabolism, thereby reducing CLA serum concentrations, and RIF concentrations might be increased by CLA co-administration. We studied the pharmacokinetics of CLA-ER at a daily dose of 15 mg/kg combined with RIF at a dose of 10 mg/kg in a subset of trial participants, and compared these to previously obtained pharmacokinetic data. Serial dried blood spot samples were obtained over a period of ten hours, and analyzed by LC-MS/MS in 30 study participants-20 in the RIF-CLA study arm, and 10 in the RIF-streptomycin study arm. Median CLA C max was 0.4 mg/L-and median AUC 3.9 mg*h/L, following 15 mg/kg CLA-ER. Compared to standard CLA dosed at 7.5 mg/kg previously, CLA-ER resulted in a non-significant 58% decrease in C max and a non-significant 30% increase in AUC. CLA co-administration did not alter RIF C max or AUC. Treatment was successful in all study participants. No effect of CLA co-administration on RIF pharmacokinetics was observed. Based on our serum concentration studies, the benefits CLA-ER over CLA immediate release are unclear.
(© 2024. The Author(s).)
Databáze: MEDLINE
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