TY - JOUR
T1 - Population pharmacokinetics of rifampicin in Mexican patients with tuberculosis
AU - Milán Segovia, R. C.
AU - Domínguez Ramírez, A. M.
AU - Jung Cook, H.
AU - Magaña Aquino, M.
AU - Vigna Pérez, M.
AU - Brundage, R. C.
AU - Romano Moreno, S.
PY - 2013/2
Y1 - 2013/2
N2 - 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.
AB - 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.
KW - NONMEM
KW - antituberculosis drug
KW - non-linear mixed-effect modelling
KW - population pharmacokinetics
KW - rifampicin
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U2 - 10.1111/jcpt.12016
DO - 10.1111/jcpt.12016
M3 - Article
C2 - 23167603
AN - SCOPUS:84871990412
SN - 0269-4727
VL - 38
SP - 56
EP - 61
JO - Journal of Clinical Pharmacy and Therapeutics
JF - Journal of Clinical Pharmacy and Therapeutics
IS - 1
ER -