title: Population pharmacokinetics of rifampicin in Mexican patients with tuberculosis.
abstract: 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.
  
  
  CONCLUSIONS
  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%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Doctorado en Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana, México. milanros@uaslp.mx
authors.forename: R C
authors.initials: RC
authors.lastname: Milán Segovia
authors.forename: A M
authors.initials: AM
authors.lastname: Domínguez Ramírez
authors.forename: H
authors.initials: H
authors.lastname: Jung Cook
authors.forename: M
authors.initials: M
authors.lastname: Magaña Aquino
authors.forename: M
authors.initials: M
authors.lastname: Vigna Pérez
authors.forename: R C
authors.initials: RC
authors.lastname: Brundage
authors.forename: S
authors.initials: S
authors.lastname: Romano Moreno
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001682:Biological Availability; D005260:Female; D006801:Humans; D008297:Male; D008800:Mexico; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D012737:Sex Factors; D014018:Tissue Distribution; D014376:Tuberculosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000904:Antibiotics, Antitubercular; D012293:Rifampin