Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis
Article first published online: 13 NOV 2012
© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 74, Issue 6, pages 971–977, December 2012
How to Cite
Bouazza, N., Pestre, V., Jullien, V., Curis, E., Urien, S., Salmon, D. and Tréluyer, J.-M. (2012), Population pharmacokinetics of clindamycin orally and intravenously administered in patients with osteomyelitis. British Journal of Clinical Pharmacology, 74: 971–977. doi: 10.1111/j.1365-2125.2012.04292.x
- Issue published online: 13 NOV 2012
- Article first published online: 13 NOV 2012
- Accepted manuscript online: 5 APR 2012 05:14AM EST
- Received; 23 January 2012; Accepted; 16 March 2012; Accepted Article Published Online; 5 April 2012
- population pharmacokinetics
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
• Clindamycin pharmacokinetics have been studied in adult patients. Rifampicin co-administration could decrease clindamycin exposure.
WHAT THIS STUDY ADDS
• This clindamycin population analysis in patients with osteomyelitis provides useful insight into the fate of this drug and shows that clindamycin clearance increases with body weight. Moreover, this study shows a potential effect of combined rifampicin on clindamycin clearance and addresses sub-therapeutic clindamycin concentrations in heavier patients.
AIMS This study was performed to describe clindamycin, administered either orally or intravenously, concentration−time courses to patients with osteomyelitis, to study the effects of different covariates on clindamycin pharmacokinetics and to simulate an optimized administration scheme.
METHODS Clindamycin concentrations were measured in 50 patients. A total of 122 plasma concentrations were available (58 from oral administration and 64 from i.v. infusion). A population pharmacokinetic model was developed with MONOLIX 4 software.
RESULTS A one compartment model adequately described the data. Clindamycin clearance increased significantly with body weight (BW). The typical population estimates (interindividual variability) for clearance, volume of distribution and absorption rate constant were 16.2 l h−1 (0.39), 70.2 l and 0.92 h−1, respectively. The bioavailability of the oral form was estimated to be 87.6%. According to BW, theoretical doses needed to reach a Cmin of 2 mg l−1 were then calculated.
CONCLUSIONS The current recommendation of 600 mg three times daily seems to be effective up to 75 kg but the dose should be raised to 900 mg three times daily thereafter. These assumptions should be prospectively confirmed.