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Degree of in vivo inhibition of human gastric and pancreatic lipases by Orlistat (Tetrahydrolipstatin, THL) in the stomach and small intestine.

Sternby, Berit LU ; Hartmann, Dieter; Borgström, Bengt LU and Nilsson, Åke LU (2002) In Clinical Nutrition 21(5). p.395-402
Abstract
BACKGROUND AND AIMS: Orlistat, a lipase inhibitor, strongly inhibits the activities of all gastric/pancreatic lipases except pancreatic phospholipase A(2)in vitro. In clinical use, for obesity treatment, it induces a variable degree of weight loss and steatorrhoéa. The aim of this study was to examine the degree of in vivo inhibition of individual gastric/pancreatic lipases by Orlistat in man, when given as a capsule or mixed into a test meal in the form of an optimal substrate for the lipases.METHODS: Twelve male volunteers were intubated twice with a triple lumen nasal-gastric-duodenal tube and were given a balanced test meal with or without 60mg Orlistat. Three conditions were compared: (a) Orlistat given as a capsule with the meal, (b)... (More)
BACKGROUND AND AIMS: Orlistat, a lipase inhibitor, strongly inhibits the activities of all gastric/pancreatic lipases except pancreatic phospholipase A(2)in vitro. In clinical use, for obesity treatment, it induces a variable degree of weight loss and steatorrhoéa. The aim of this study was to examine the degree of in vivo inhibition of individual gastric/pancreatic lipases by Orlistat in man, when given as a capsule or mixed into a test meal in the form of an optimal substrate for the lipases.METHODS: Twelve male volunteers were intubated twice with a triple lumen nasal-gastric-duodenal tube and were given a balanced test meal with or without 60mg Orlistat. Three conditions were compared: (a) Orlistat given as a capsule with the meal, (b) Orlistat mixed into the test meal before ingestion, and (c) test meal without Orlistat. Samples were collected at six 30min intervals, from stomach, mid-duodenum, and ligament of TreitY. Activities and immune-reactive masses of gastric lipase, pancreatic lipase, carboxyl ester lipase, colipase, and mass of non-polar lipid classes were determined.RESULTS: In vivo effects on the enzyme activities were more pronounced when Orlistat was mixed with the meal than when given as a capsule (7%, 10%, 1% vs 49%, 54%, 34% of normal activity), respectively. Despite efficient inhibition of the lipases, an extensive hydrolysis of the emulsified lipids of the test meal occurred. Orlistat did not affect the immune-reactive amounts of lipases.CONCLUSIONS: Orlistat causes a pronounced in vivo inhibition of gastric and pancreatic lipases in humans. The mixing with the substrate and the fact that little residual lipase activity is necessary to hydrolyse optimally emulsified lipids are likely to be limiting factors for the effect of the drug in clinical practice. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Nutrition
volume
21
issue
5
pages
395 - 402
publisher
Elsevier
external identifiers
  • wos:000178689100006
  • pmid:12381337
  • scopus:0036800371
ISSN
1532-1983
DOI
10.1054/clnu.2002.0565
language
English
LU publication?
yes
id
a405e183-c68f-4abd-bc02-9863d7da8ef4 (old id 110631)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12381337&dopt=Abstract
date added to LUP
2007-06-29 15:53:47
date last changed
2017-08-20 04:30:02
@article{a405e183-c68f-4abd-bc02-9863d7da8ef4,
  abstract     = {BACKGROUND AND AIMS: Orlistat, a lipase inhibitor, strongly inhibits the activities of all gastric/pancreatic lipases except pancreatic phospholipase A(2)in vitro. In clinical use, for obesity treatment, it induces a variable degree of weight loss and steatorrhoéa. The aim of this study was to examine the degree of in vivo inhibition of individual gastric/pancreatic lipases by Orlistat in man, when given as a capsule or mixed into a test meal in the form of an optimal substrate for the lipases.METHODS: Twelve male volunteers were intubated twice with a triple lumen nasal-gastric-duodenal tube and were given a balanced test meal with or without 60mg Orlistat. Three conditions were compared: (a) Orlistat given as a capsule with the meal, (b) Orlistat mixed into the test meal before ingestion, and (c) test meal without Orlistat. Samples were collected at six 30min intervals, from stomach, mid-duodenum, and ligament of TreitY. Activities and immune-reactive masses of gastric lipase, pancreatic lipase, carboxyl ester lipase, colipase, and mass of non-polar lipid classes were determined.RESULTS: In vivo effects on the enzyme activities were more pronounced when Orlistat was mixed with the meal than when given as a capsule (7%, 10%, 1% vs 49%, 54%, 34% of normal activity), respectively. Despite efficient inhibition of the lipases, an extensive hydrolysis of the emulsified lipids of the test meal occurred. Orlistat did not affect the immune-reactive amounts of lipases.CONCLUSIONS: Orlistat causes a pronounced in vivo inhibition of gastric and pancreatic lipases in humans. The mixing with the substrate and the fact that little residual lipase activity is necessary to hydrolyse optimally emulsified lipids are likely to be limiting factors for the effect of the drug in clinical practice.},
  author       = {Sternby, Berit and Hartmann, Dieter and Borgström, Bengt and Nilsson, Åke},
  issn         = {1532-1983},
  language     = {eng},
  number       = {5},
  pages        = {395--402},
  publisher    = {Elsevier},
  series       = {Clinical Nutrition},
  title        = {Degree of in vivo inhibition of human gastric and pancreatic lipases by Orlistat (Tetrahydrolipstatin, THL) in the stomach and small intestine.},
  url          = {http://dx.doi.org/10.1054/clnu.2002.0565},
  volume       = {21},
  year         = {2002},
}