Long-term systemic exposure of orlistat, a lipase inhibitor, and its metabolites in obese patients

J Clin Pharmacol. 1999 Jan;39(1):41-6. doi: 10.1177/00912709922007543.


Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract; its systemic exposure is not required for its efficacy. However, knowledge of the extent of its systemic exposure is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening in obese patients was carried out by monitoring plasma concentrations of unchanged orlistat and its metabolites in five key double-blind, placebo-controlled phase II/III studies. Results of these studies involving the monitoring of plasma samples indicate that detection of intact orlistat in plasma was sporadic, and measurable concentrations were low (< 10 ng/mL or 0.02 microM) without evidence of accumulation, which is consistent with minimal absorption. It is concluded that systemic exposure of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Controlled Clinical Trial
  • Multicenter Study

MeSH terms

  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacokinetics*
  • Gastrointestinal Diseases / chemically induced
  • Humans
  • Lactones / adverse effects
  • Lactones / metabolism
  • Lactones / pharmacokinetics*
  • Lipase / antagonists & inhibitors*
  • Obesity / drug therapy*
  • Orlistat
  • Time Factors
  • Treatment Outcome


  • Enzyme Inhibitors
  • Lactones
  • Orlistat
  • Lipase