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Klis, Sandor-Adrian, Stienstra, Ymkje, Abass, Kabiru M., Abottsi, Justice, Mireku, Samuel O., Alffenaar, Jan-Willem and van der Werf, Tjip S. (2024) 'Pharmacokinetics of extended-release clarithromycin in patients with Mycobacterium ulcerans infection'. Scientific Reports, Vol 14, Issue 1, e19963.
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41598_2024_Article_70890.pdf - Published Version Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (1MB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Subjects: | WC Communicable Diseases > Infection. Bacterial Infections > Other Bacterial Infections. Zoonotic Bacterial Infections > WC 302 Actinomycetales infections. Mycobacterium infections |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department |
| Digital Object Identifer (DOI): | https://doi.org/10.1038/s41598-024-70890-w |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 16 Sep 2024 10:28 |
| Last Modified: | 16 Sep 2024 10:28 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/25231 |
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