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Long‐Term Systemic Exposure of Orlistat, a Lipase Inhibitor, and Its Metabolites in Obese Patients
Author(s) -
Zhi Jianguo,
Mulligan Thomas E.,
Hauptman Jonathan B.
Publication year - 1999
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/00912709922007543
Subject(s) - orlistat , pharmacokinetics , medicine , lipase , placebo , population , pharmacology , pharmacoeconomics , obesity , chemistry , weight loss , enzyme , biochemistry , intensive care medicine , alternative medicine , environmental health , pathology
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 μM) 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.