Review of Limited Systemic Absorption of Orlistat, a Lipase Inhibitor, in Healthy Human Volunteers

  title={Review of Limited Systemic Absorption of Orlistat, a Lipase Inhibitor, in Healthy Human Volunteers},
  author={Jianguo Zhi and Angela T. Melia and Herwig Eggers and Regine Joly and Indravadan H. Patel},
  journal={The Journal of Clinical Pharmacology},
  • J. Zhi, A. Melia, +2 authors I. Patel
  • Published 1 November 1995
  • Chemistry, Medicine
  • The Journal of Clinical Pharmacology
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… Expand
Long‐Term Systemic Exposure of Orlistat, a Lipase Inhibitor, and Its Metabolites in Obese Patients
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), which is consistent with minimal absorption. Expand
The pharmacodynamic equivalence of Orlistat 60 mg capsule. An open label, balanced, randomized, multiple-dose, cross-over pharmacodynamic end-point bioequivalence study in healthy, adult, human Asian Indian subjects under fed conditions
Results from this study suggest that the test formulation of Orlistat capsule is bioequivalent to the reference marketed Alli™ when administered to healthy volunteers as a multiple dose under fed conditions. Expand
Lack of Effect of Orlistat on the Bioavailability of a Single Dose of Nifedipine Extended‐Release Tablets (Procardia XL) in Healthy Volunteers
The 90% confidence intervals for the ratio of geometric least‐square means for maximum concentration (Cmax) and area under the concentration‐time curve (AUCo‐t) indicate that the bioavailability of nifedipine was not altered by treatment with orlistat. Expand
Orlistat, a New Lipase Inhibitor for the Management of Obesity
The potential for severe gastrointestinal discomfort and the modest degree of weight loss may limit the agent's clinical utility, while its long‐term safety and effectiveness for weight maintenance, cost‐effectiveness of treatment, and overall reduction in obesity‐related morbidity and mortality remain to be determined. Expand
Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers.
The inhibition of digestive lipases by the antiobesity drug Orlistat along with lipolysis levels and fecal fat excretion were measured in healthy humans and found to be a powerful gastric lipase inhibitor, greatly reducing gastriclipolysis of solid and liquid meals. Expand
Intestinal delivery in a long-chain fatty acid formulation enables lymphatic transport and systemic exposure of orlistat.
Administration of orlistat in a long-chain fatty acid formulation promotes lymph and systemic uptake which may enable treatment of diseases associated with elevated systemic PL activity. Expand
Metabolic Profiles of Minimally Absorbed Orlistat in Obese/Overweight Volunteers
The disposition of orlistat appears to be similar between normal and obese/overweight subjects. Expand
The Effect of Orlistat, an Inhibitor of Dietary Fat Absorption, on the Pharmacokinetics of β‐Carotene in Healthy Volunteers
It was concluded that two thirds of a supplemental dose ofβ‐carotene will be absorbed during orlistat treatment; this may be sufficient to achieve physiologic levels of β‐ carotene with an appropriate dose of β-carotenes, should supplementation be needed in obese patients who have developed β‐Carotene deficiency during therapy with or listat. Expand
Orlistat: a review of its use in the management of obesity.
Orlistat in conjunction with a hypocaloric diet has been shown to induce clinically significant weight loss in keeping with current guidelines for the management of obesity and its acceptable tolerability profile and lack of systemic adverse events make it an attractive option in the treatment of obesity. Expand
Orlistat — A Novel Weight Loss Therapy
Preliminary data from clinical trials suggest that orlistat may be beneficial in patients with comorbid conditions related to obesity, such as diabetes and hyperlipidemia, however, further studies during postmarketing surveillance are needed to fully establish orlistsat's long-term benefits and safety. Expand


Comparison of the Inhibition of Dietary Fat Absorption by Full Versus Divided Doses of Orlistat
Changing the mode of administration of orlistat, within the dose regimens investigated, does not affect its pharmacologic efficacy. Expand
Retrospective population‐based analysis of the dose‐response (fecal fat excretion) relationship of orlistat in normal and obese volunteers
The model‐fitting suggests the existence of a steep portion of the dose‐response curve up to approximately 400 mg/day, with a subsequent tendency to plateau at higher doses, which was instrumental in identifying appropriate doses to be used in therapeutic trials for weight loss in obese patients. Expand
Lipase inhibition: a novel concept in the treatment of obesity.
  • M. Drent, E. A. van der Veen
  • Medicine
  • International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity
  • 1993
Orlistat (Ro 18-0647) is an inhibitor of gastric, carboxylester and pancreatic lipase and specifically reduces the absorption of dietary fat due to the inhibition of triglyceride hydrolysis. OrlistatExpand
Comparison of Galenic Formulations of Orlistat (Tetrahydrolipstatin)
The 14C-breath test proved to be a reliable and convenient method to assess fat absorption in relative terms and thus to compare galenic formulations of orlistat. Expand
Effect on dietary fat absorption of orlistat, administered at different times relative to meal intake.
It was concluded that, within the time period investigated, the pharmacological effect of O is not critically dependent on the time of dosing relative to meals. Expand
Initial studies in humans with the novel gastrointestinal lipase inhibitor Ro 18-0647 (tetrahydrolipstatin).
Initial studies in humans have shown that Ro 18-0647 can reliably increase fecal fat excretion and further research must be conducted to determine whether clinical endpoints of weight loss or cholesterol lowering can be produced by using this new pharmacologic principle. Expand
Influence of Dietary Composition on the Inhibition of Fat Absorption by Orlistat
Dietary fibre content and accessibility of fat had no relevant effect on the inhibition of fat absorption by orlistat, and the statistically significant difference in total faecal fat between intracellular fat and extracellular fat groups was not regarded as clinically relevant. Expand
Mode of action of tetrahydrolipstatin: a derivative of the naturally occurring lipase inhibitor lipstatin.
  • B. Borgström
  • Chemistry, Medicine
  • Biochimica et biophysica acta
  • 1988
Tetrahydrolipstatin is a specific lipase inhibitor derived from lipstatin, a lipid produced by Streptomyces toxytricini that inhibits human gastric lipase, carboxyl ester lipase (cholesterol esterase) of pancreatic origin and the closely related bile-salt-stimulated lipase of human milk. Expand
Inhibition of pancreatic lipase in vitro by the covalent inhibitor tetrahydrolipstatin.
Tetrahydrolipstatin inhibits pancreatic lipase from several species, including man, with comparable potency and is a selective inhibitor of lipase; other hydrolases tested were at least a thousand times less potently inhibited. Expand
JHG: Comparison of galenic formulations of orlistat (tetrahydrolipstatin): a pharmacological approach
  • Drug Invest
  • 1993