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J Clin Pharm Ther. 2013 Feb;38(1):56-61. doi: 10.1111/jcpt.12016. Epub 2012 Nov 20.

Population pharmacokinetics of rifampicin in Mexican patients with tuberculosis.

Author information

1
Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, México. milanros@uaslp.mx

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 V(d)/F = 50·1 L (1·29 as high for males), absorption rate constant K(aA) = 0·391/h, K(aB,C,D) = 2·70/h, relative bioavailability F(A) = 0·468, F(B,C,D) = 1, lag time in the absorption phase T(lag) = 0·264 h. The final model improved the precision on the parameter estimates (CL/F, V(d) /F and K(a) 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 V(d) /F whereas the pharmaceutical formulation was associated with changes in F and altered the K(a) . The validation data set showed that the model could be used in clinical practice for Bayesian dose adjustment of RIF in TB patients.

PMID:
23167603
DOI:
10.1111/jcpt.12016
[Indexed for MEDLINE]

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