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- Title
Population pharmacokinetics of rifampicin in Mexican patients with tuberculosis.
- Authors
Milán Segovia, R. C.; Domínguez Ramírez, A. M.; Jung Cook, H.; Magaña Aquino, M.; Vigna Pérez, M.; Brundage, R. C.; Romano Moreno, S.
- Abstract
What is known and Objective: Rifampicin (RIF) shows wide variability in its pharmacokinetics. The purpose of this study was to develop and validate a population pharmacokinetic model to characterize the inter- and intra-individual variability in pharmacokinetic parameters of RIF in Mexican patients. Methods: Ninety-four patients receiving antituberculosis therapy participated in this prospective study. Plasma concentration-time data were described using a one-compartment model with lag time, absorption and first-order elimination. The potential influence of demographic and clinical characteristics of the patients, and the pharmaceutical formulation (A, B, C and D) on the pharmacokinetics parameters, was evaluated by non-linear mixed-effect modelling ( nonmem). Seventy-seven additional patients participated in the validation of the model. Results and Discussion: The final population pharmacokinetic model obtained was as follows: apparent clearance CL/ F = 8·17 L/h (1·40 as high for males), apparent distribution volume Vd/ F = 50·1 L (1·29 as high for males), absorption rate constant KaA = 0·391/h, KaB,C,D =2·70/h, relative bioavailability FA = 0·468, FB,C,D =1, lag time in the absorption phase Tlag = 0·264 h. The final model improved the precision on the parameter estimates (CL/ F, Vd/ F and Ka by 31·9%, 16·7% and 92·9%, respectively). The residual variability was 27·3%. What is new and Conclusion: Gender was associated with changes in CL/ F and Vd/ F whereas the pharmaceutical formulation was associated with changes in F and altered the Ka. The validation data set showed that the model could be used in clinical practice for Bayesian dose adjustment of RIF in TB patients.
- Subjects
MEXICO; DRUG therapy for tuberculosis; CONFIDENCE intervals; HIGH performance liquid chromatography; LONGITUDINAL method; RESEARCH funding; RIFAMPIN; SEX distribution; STATISTICS; DATA analysis; DATA analysis software; STATISTICAL models; DESCRIPTIVE statistics
- Publication
Journal of Clinical Pharmacy & Therapeutics, 2013, Vol 38, Issue 1, p56
- ISSN
0269-4727
- Publication type
Article
- DOI
10.1111/jcpt.12016