Document Detail

Inhibition of gastrointestinal lipolysis by Orlistat during digestion of test meals in healthy volunteers.
MedLine Citation:
PMID:  11408251     Owner:  NLM     Status:  MEDLINE    
The inhibition of digestive lipases by the antiobesity drug Orlistat along with lipolysis levels and fecal fat excretion were measured in healthy humans. Orlistat was found to be a powerful gastric lipase inhibitor, achieving 46.6--91.4% enzyme inhibition and thus greatly reducing gastric lipolysis of solid and liquid meals (11--33% of respective controls). Gastric lipase inhibition by Orlistat was extremely fast (half-inhibition time < 1 min). Duodenal lipolysis was reduced significantly by Orlistat given with the solid meal (32.6--37.6% of controls) but was only slightly reduced by Orlistat given with the liquid meal (74.5--100% of controls). Human pancreatic lipase (HPL) inhibition was found to be high (51.2--82.6%), however, regardless of the meal. These paradoxical results were explained when in vitro lipolysis experiments were performed. The rates of HPL inhibition by Orlistat were found to be similar with both types of meals (half-inhibition time 5--6 min), but the preemulsified triglycerides of the liquid meal were rapidly hydrolyzed by HPL before the enzyme was significantly inhibited by Orlistat. With the solid meal, the rate of hydrolysis of the meal triglycerides by HPL was slower than the rate of HPL inhibition by Orlistat. As predicted from the previous results, the effects of Orlistat on fat excretion levels were found to be much greater with the solid (40.5--57.4% of ingested fat) than with the liquid (4.2--18.8%) test meal.
F Carrière; C Renou; S Ransac; V Lopez; J De Caro; F Ferrato; A De Caro; A Fleury; P Sanwald-Ducray; H Lengsfeld; C Beglinger; P Hadvary; R Verger; R Laugier
Publication Detail:
Type:  Clinical Trial; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  281     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2001-06-15     Completed Date:  2001-07-19     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G16-28     Citation Subset:  IM    
Laboratoire de Lipolyse Enzymatique, Centre National de la Recherche Scientifique, Institut de Biologie Structurale et Microbiologie, F-13402 Marseille Cedex 20, France.
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MeSH Terms
Anti-Obesity Agents / administration & dosage*
Dietary Fats / administration & dosage,  pharmacokinetics
Duodenogastric Reflux / metabolism
Duodenum / metabolism
Gastric Juice
Intubation, Gastrointestinal
Lactones / administration & dosage*
Lipase / antagonists & inhibitors*
Lipolysis / drug effects*
Middle Aged
Obesity / drug therapy,  metabolism
Pancreas / metabolism
Pancreatic Juice
Stomach / metabolism
Reg. No./Substance:
0/Anti-Obesity Agents; 0/Dietary Fats; 0/Lactones; 96829-58-2/orlistat; EC

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