Pharmacokinetics of extended-release clarithromycin in patients with Mycobacterium ulcerans infection.
Sci Rep
; 14(1): 19963, 2024 08 28.
Article
en En
| MEDLINE
| ID: mdl-39198495
ABSTRACT
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 Cmax 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 Cmax and a non-significant 30% increase in AUC. CLA co-administration did not alter RIF Cmax 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Rifampin
/
Claritromicina
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Mycobacterium ulcerans
/
Preparaciones de Acción Retardada
/
Úlcera de Buruli
Límite:
Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos
Pais de publicación:
Reino Unido