title: In vitro-in vivo Pharmacokinetic correlation model for quality assurance of antiretroviral drugs.
abstract: BACKGROUND
  The in vitro-in vivo pharmacokinetic correlation models (IVIVC) are a fundamental part of the drug discovery and development process. The ability to accurately predict the in vivo pharmacokinetic profile of a drug based on in vitro observations can have several applications during a successful development process.
  
  
  OBJECTIVE
  To develop a comprehensive model to predict the in vivo absorption of antiretroviral drugs based on permeability studies, in vitro and in vivo solubility and demonstrate its correlation with the pharmacokinetic profile in humans.
  
  
  METHODS
  Analytical tools to test the biopharmaceutical properties of stavudine, lamivudine y zidovudine were developed. The kinetics of dissolution, permeability in caco-2 cells and pharmacokinetics of absorption in rabbits and healthy volunteers were evaluated.
  
  
  RESULTS
  The cumulative areas under the curve (AUC) obtained in the permeability study with Caco-2 cells, the dissolution study and the pharmacokinetics in rabbits correlated with the cumulative AUC values in humans. These results demonstrated a direct relation between in vitro data and absorption, both in humans and in the in vivo model.
  
  
  CONCLUSIONS
  The analytical methods and procedures applied to the development of an IVIVC model showed a strong correlation among themselves. These IVIVC models are proposed as alternative and cost/effective methods to evaluate the biopharmaceutical properties that determine the bioavailability of a drug and their application includes the development process, quality assurance, bioequivalence studies and pharmacosurveillance.
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Rojas Gómez
authors.affiliation: Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.
authors.forename: Piedad
authors.initials: P
authors.lastname: Restrepo Valencia
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D018938:Caco-2 Cells; D006801:Humans; D019259:Lamivudine / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008954:Models, Biological; D010539:Permeability; D011817:Rabbits; D012995:Solubility; D013045:Species Specificity; D018119:Stavudine / Q000737:chemistry / Q000493:pharmacokinetics*; D055815:Young Adult; D015215:Zidovudine / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D019380:Anti-HIV Agents; D019259:Lamivudine; D015215:Zidovudine; D018119:Stavudine
keywords: antiretrovirals; bioavailability; correlation; dissolution; permeability; pharmacokinetics