Pharmacokinetic evaluation of the possible interaction between selected concomitant medications and orlistat at steady state in healthy subjects

J Clin Pharmacol. 2002 Sep;42(9):1011-9.


To investigate the influence of orlistat on the pharmacokinetics of selected concomitant medications (amitriptyline, atorvastatin, cyclosporine, losartan, metformin, phentermine, and sibutramine) at or within two-fold of therapeutic doses, open-label, multiple-dose (for 6 or 7 days), randomized, two-period (except for cyclosporine, for which a three-way crossover design was used) crossover studies were performed in healthy volunteers ages 18 to 65 years, with a body mass index between 18 and 30 kg/m2. At steady state, blood samples were taken for measuring plasma concentrations of interacting drugs and/or active metabolites. Subjects were also evaluated for adverse events, vital signs, and clinical and laboratory safety. Treatments were compared for AUC0-24, Cmax, tmax, and t1/2 of selected concomitant medications (parent drugs and/or active metabolites). ANOVA was performed to assess the significance of the carry-over effect and provide the variance estimate for the 90% confidence intervals (CIs). With the exception of cyclosporine, whose absorption was reduced by approximately one-third, the results of the statistical analysis demonstrated equivalencefor the two primary parameters for all drugs studied: ratios of the log-transformed means for both AUC and Cmax were close to 1.00, with 90% CIs contained entirely within the bioequivalence region of 0.80 to 1.25; there were no clinically significant differences in t1/2 and tmax. There was a higher incidence of adverse events under treatment B (selective concomitant medications and orlistat) than under treatment A (selective concomitant medications alone); most of this difference was due to expected gastrointestinal adverse events known to occur with orlistat. Other adverse events were sporadic and unremarkable. All adverse events were either mild or moderate in intensity. There were no clinically relevant changes in vital signs or laboratory values. In conclusion, except for cyclosporine, there was no effect of orlistat on the pharmacokinetics of selective concomitant medications when these drugs were taken concomitantly with orlistat.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / blood
  • Anti-Obesity Agents / pharmacokinetics*
  • Area Under Curve
  • Cross-Over Studies
  • Double-Blind Method
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Lactones / adverse effects
  • Lactones / blood
  • Lactones / pharmacokinetics*
  • Male
  • Middle Aged
  • Orlistat


  • Anti-Obesity Agents
  • Lactones
  • Orlistat