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Population pharmacokinetics of daptomycin in patients with bone and joint infection: minimal effect of rifampicin co-administration and confirmation of a sex difference

Romain Garreau 1, 2 Romain Bricca 3, 2 Marie-Claude Gagnieu 1, 2 Sandrine Roux 4, 5, 2 Anne Conrad 4, 5, 6, 2 Laurent Bourguignon 1, 6, 7, 2 Tristan Ferry 4, 5, 6, 8, 2 Sylvain Goutelle 1, 6, 7, 2 Florent Valour 2 Thomas Perpoint 2 Patrick Miailhes 2 Florence Ader 2 Agathe Becker 2 Claire Triffault-Fillit 2 Cécile Pouderoux 2 Nicolas Benech 2 Pierre Chauvelot 2 Marielle Perry 2 Fatiha Daoud 2 Johanna Lippman 2 Evelyne Braun 2 Christian Chidiac 2 Elvire Servien 2 Sébastien Lustig 2 Cécile Batailler 2 Stanislas Gunst 2 Axel Schmidt 2 Matthieu Malatray 2 Elliot Sappey-Marinier 2 Michel-Henry Fessy 2 Anthony Viste 2 Jean-Luc Besse 2 Philippe Chaudier 2 Lucie Louboutin 2 Quentin Ode 2 Adrien van Haecke 2 Marcelle Mercier 2 Vincent Belgaid 2 Arnaud Walch 2 Sébastien Martres 2 Franck Trouillet 2 Cédric Barrey 2 Ali Mojallal 2 Sophie Brosset 2 Camille Hanriat 2 Hélène Person 2 Nicolas Sigaux 2 Philippe Céruse 2 Carine Fuchsmann 2 Frédéric Aubrun 2 Mikhail Dziadzko 2 Caroline Macabéo 2 Frederic Laurent 2 Laetitia Beraud 2 Tiphaine Roussel-Gaillard 2 Céline Dupieux 2 Camille Kolenda 2 Jérôme Josse 2 Marie Brevet 2 Alexis Trecourt 2 Fabien Craighero 2 Loic Boussel 2 Jean-Baptiste Pialat 2 Isabelle Morelec 2 Michel Tod 2 Eugénie Mabrut 2
Abstract : Background Daptomycin is increasingly used in the treatment of bone and joint infection (BJI), but its pharmacokinetics (PK) and dosage requirements have not been thoroughly investigated in this indication. Daptomycin may be co-administered with rifampicin, which raises questions about a potential drug interaction. Objectives To investigate the population PK and dosage requirements of daptomycin in patients with BJI, and examine the influence of rifampicin co-administration. Methods A population approach was used to analyse PK data from patients who received daptomycin in our regional reference for BJI. We examined the influence of available covariates, including rifampicin co-administration on daptomycin PK. Simulations performed with the final model investigated the influence of dosages and covariates on PTA for both efficacy and safety. Results A total of 1303 daptomycin concentrations from 183 patients were analysed. A two-compartment model best described the data. Significant intra-individual variability was observed. Daptomycin clearance was influenced by renal function and sex, with females having a 26% lower typical clearance than males. Central volume of distribution (V1) was influenced by body weight, age, sex and rifampicin co-administration. Typical V1 was 11% lower in patients who were co-administered rifampicin. In PK/PD simulations, sex influenced the probability of AUC24/MIC target attainment, while rifampicin had a marginal effect. Conclusions A daptomycin dosage of 8 mg/kg/24 h in women and 10 mg/kg/24 h in men should optimize efficacy but may lead to excessive trough concentrations in many patients, especially in women. Therapeutic drug monitoring appears necessary for precision dosing of daptomycin.
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https://hal.umontpellier.fr/hal-03624877
Contributeur : Nathalie Salvy-Cordoba Connectez-vous pour contacter le contributeur
Soumis le : mercredi 30 mars 2022 - 15:17:08
Dernière modification le : vendredi 1 avril 2022 - 03:43:31

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Romain Garreau, Romain Bricca, Marie-Claude Gagnieu, Sandrine Roux, Anne Conrad, et al.. Population pharmacokinetics of daptomycin in patients with bone and joint infection: minimal effect of rifampicin co-administration and confirmation of a sex difference. Journal of Antimicrobial Chemotherapy, Oxford University Press (OUP), 2021, 76 (5), pp.1250-1257. ⟨10.1093/jac/dkab006⟩. ⟨hal-03624877⟩

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