Influence of the clindamycin administration route on the magnitude of clindamycin-rifampicin interaction: a prospective pharmacokinetic study

Autor: Anne-Sophie Jannot, Sophie Magreault, Vincent Jullien, Dominique Salmon, Valérie Zeller, Eliane Billaud, Laurence Salomon, Beate Heym, Simon Marmor, Marie-Dominique Kitzis
Přispěvatelé: Groupe Hospitalier Diaconesses Croix Saint-Simon, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier Saint-Joseph [Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Health data- and model- driven Knowledge Acquisition (HeKA), Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris Cité (UPCité), GHU AP-HP Centre Université de Paris, Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Groupe Hospitalier Universitaire Paris Seine-Saint-Denis (GHUPSSD)
Rok vydání: 2021
Předmět:
Zdroj: Clinical Microbiology and Infection
Clinical Microbiology and Infection, 2021, 27 (12), pp.1857.e1-1857.e7. ⟨10.1016/j.cmi.2021.04.017⟩
ISSN: 1469-0691
1198-743X
DOI: 10.1016/j.cmi.2021.04.017⟩
Popis: Objectives An important clindamycin–rifampicin pharmacokinetic (PK) interaction has been reported, but the potential influence of the clindamycin administration route on that interaction is unknown. This prospective, observational, comparative PK study was undertaken to characterize and analyse the impact of the route, comparing the rifampicin enzyme-inductor effects on clindamycin clearance (CLclin) for oral versus intravenous (IV) administration. Methods Patients with bone-and-joint infections (BJIs) were treated with clindamycin monotherapy (n = 20) or clindamycin–rifampicin combination therapy (n = 19). Patients received continuous IV clindamycin infusion for 2–6 weeks, followed by an oral regimen. Liquid chromatography–mass spectrometry was used to measure plasma clindamycin concentrations at the end of IV and after 2 weeks of oral treatment. The ratios of the mean CLclin for the combination and monotherapy groups were calculated for IV (Riv) and oral (Rpo) routes, with the final ratio, Rf = Rpo/Riv, representing the fold change of the rifampicin-inducing effect from the IV to the oral route. Results Comparing monotherapy with combination-therapy groups, the former's median steady-state concentration was two-fold higher after IV administration (8.49 versus 3.82 mg/L, p Conclusion The magnitude of this interaction was markedly increased by oral intake, questioning the use of oral treatment for difficult-to-treat infections like BJIs. Nevertheless, the clindamycin–rifampicin combination seems possible provided that clindamycin is administered by continuous IV infusion.
Databáze: OpenAIRE
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