Population pharmacokinetics of rifampicin in Mexican patients with tuberculosis

R. C. Milán Segovia, A. M. Domínguez Ramírez, H. Jung Cook, M. Magaña Aquino, M. Vigna Pérez, R. C. Brundage, S. Romano Moreno

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)56-61
Number of pages6
JournalJournal of Clinical Pharmacy and Therapeutics
Volume38
Issue number1
DOIs
StatePublished - Feb 2013

Keywords

  • NONMEM
  • antituberculosis drug
  • non-linear mixed-effect modelling
  • population pharmacokinetics
  • rifampicin

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