1. Population pharmacokinetics of daptomycin in patients with bone and joint infection: minimal effect of rifampicin co-administration and confirmation of a sex difference
- Author
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Garreau, Romain, Bricca, Romain, Gagnieu, Marie-Claude, Roux, Sandrine, Conrad, Anne, Bourguignon, Laurent, Ferry, Tristan, Goutelle, Sylvain, Valour, Florent, Perpoint, Thomas, Miailhes, Patrick, Ader, Florence, Becker, Agathe, Triffault-Fillit, Claire, Pouderoux, Cécile, Benech, Nicolas, Chauvelot, Pierre, Perry, Marielle, Daoud, Fatiha, Lippman, Johanna, Braun, Evelyne, Chidiac, Christian, Servien, Elvire, Lustig, Sébastien, Batailler, Cécile, Gunst, Stanislas, Schmidt, Axel, Malatray, Matthieu, Sappey-Marinier, Elliot, Fessy, Michel-Henry, Viste, Anthony, Besse, Jean-Luc, Chaudier, Philippe, Louboutin, Lucie, Ode, Quentin, van Haecke, Adrien, Mercier, Marcelle, Belgaid, Vincent, Walch, Arnaud, Martres, Sébastien, Trouillet, Franck, Barrey, Cédric, Mojallal, Ali, Brosset, Sophie, Hanriat, Camille, Person, Hélène, Sigaux, Nicolas, Céruse, Philippe, Fuchsmann, Carine, Aubrun, Frédéric, Dziadzko, Mikhail, Macabéo, Caroline, Laurent, Frederic, Beraud, Laetitia, Roussel-Gaillard, Tiphaine, Dupieux, Céline, Kolenda, Camille, Josse, Jérôme, Brevet, Marie, Trecourt, Alexis, Craighero, Fabien, Boussel, Loic, Pialat, Jean-Baptiste, Morelec, Isabelle, Tod, Michel, Mabrut, Eugénie, Hospices Civils de Lyon (HCL), Lyon Bone and Joint Infection Study Group (BJI), Hôpital Nord-Ouest de Villefranche-sur-Saône, Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre interrégional de référence Rhône-Alpes - Auvergne des infections ostéo-articulaires complexes, Institut des Sciences Pharmaceutiques et Biologiques (ISPB), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL)
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Male ,0301 basic medicine ,Microbiology (medical) ,medicine.medical_specialty ,030106 microbiology ,Population ,MESH: Daptomycin ,03 medical and health sciences ,0302 clinical medicine ,Daptomycin ,Pharmacokinetics ,MESH: Drug Monitoring ,Internal medicine ,MESH: Anti-Bacterial Agents ,medicine ,polycyclic compounds ,Humans ,Pharmacology (medical) ,030212 general & internal medicine ,Dosing ,education ,Pharmacology ,Volume of distribution ,Sex Characteristics ,education.field_of_study ,MESH: Humans ,medicine.diagnostic_test ,business.industry ,Drug interaction ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,bacterial infections and mycoses ,MESH: Rifampin ,MESH: Male ,Anti-Bacterial Agents ,Infectious Diseases ,Therapeutic drug monitoring ,Female ,Drug Monitoring ,Rifampin ,business ,MESH: Female ,Rifampicin ,medicine.drug ,MESH: Sex Characteristics - 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.
- Published
- 2021