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Review of Limited Systemic Absorption of Orlistat, a Lipase Inhibitor, in Healthy Human Volunteers
Author(s) -
Zhi Jianguo,
Melia Angela T.,
Eggers Herwig,
Joly Raymond,
Patel Indravadan H.
Publication year - 1995
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 - 10.1002/j.1552-4604.1995.tb04034.x
Subject(s) - orlistat , pharmacokinetics , medicine , absorption (acoustics) , pharmacology , population , excretion , endocrinology , obesity , weight loss , physics , environmental health , acoustics
Orlistat, a lipase inhibitor, acts locally in the gastrointestinal tract. Systemic absorption is not required for its efficacy, but knowledge of the extent of its systemic absorption is important for its safe use in obese patients, the intended target population. Pharmacokinetic screening was carried out by monitoring plasma concentrations of unchanged orlistat in 25 phase 1 studies (including two mass balance studies) in normal and obese healthy volunteers. The results of these studies indicate an extremely low degree of systemic absorption for orlistat when administered with a hypocaloric, well‐balanced diet with 20% to 30% of calories derived from fat (50–80 gm). To further characterize the pharmacokinetics and excretion pathways of orlistat, two mass balance studies using 14 C‐labeled orlistat were conducted. After oral dosing of radiolabeled orlistat with a fatty meal (28–30 gm fat), almost the entire dose was recovered from fecal samples; little was found in plasma and urine. It is concluded that systemic absorption of orlistat is negligible; at a clinically efficacious dose level, orlistat is unlikely to produce systemic lipase inhibition.