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Disposition of venlafaxine enantiomers in rats with hepatic encephalopathy after chronic drug treatment.

Wikell, Cecilia LU ; Eap, Chin B; Josefsson, Martin; Apelqvist, Gustav; Ahlner, Johan; Baumann, Pierre and Bengtsson, Finn (2002) In Chirality 14(4). p.347-350
Abstract
Portacaval shunted (PCS) rats, a model of hepatic encephalopathy, and control animals were administered racemic venlafaxine for 14 days (10 mg/kg). The levels of the S- and R-enantiomers and the S/R-enantiomer ratios of venlafaxine and its metabolites were assessed by an enantiomer-selective chromatographic assay in serum, brain parenchyma, and brain dialysate of both groups. Higher levels of the S- and R-enantiomers of venlafaxine were found in serum and brain of PCS vs. normal rats (median values of S- and R-venlafaxine in serum: 290 and 201 nM in PCS; 97 and 66 nM in normal rats; median values of S- and R-venlafaxine in cortex: 956 and 939 nM in PCS; 357 and 318 nM in normal rats). Interestingly, similar S/R-venlafaxine ratios were... (More)
Portacaval shunted (PCS) rats, a model of hepatic encephalopathy, and control animals were administered racemic venlafaxine for 14 days (10 mg/kg). The levels of the S- and R-enantiomers and the S/R-enantiomer ratios of venlafaxine and its metabolites were assessed by an enantiomer-selective chromatographic assay in serum, brain parenchyma, and brain dialysate of both groups. Higher levels of the S- and R-enantiomers of venlafaxine were found in serum and brain of PCS vs. normal rats (median values of S- and R-venlafaxine in serum: 290 and 201 nM in PCS; 97 and 66 nM in normal rats; median values of S- and R-venlafaxine in cortex: 956 and 939 nM in PCS; 357 and 318 nM in normal rats). Interestingly, similar S/R-venlafaxine ratios were observed in PCS and normal rats both in serum (S/R = 1.4) and brain compartments (S/R = l.0-1.1). These findings may have clinical relevance for the safety of venlafaxine in chronic hepatic encephalopathy. (Less)
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keywords
Cyclohexanols : administration & dosage, Cyclohexanols : chemistry, Cyclohexanols : pharmacokinetics, Disease Models, Animal, Hepatic Encephalopathy : drug therapy, Hepatic Encephalopathy : metabolism, Human, Male, Portacaval Shunt, Rats, Surgical, Sprague-Dawley, Safety, Stereoisomerism, Brain : metabolism, Second-Generation : pharmacokinetics, Second-Generation : chemistry, Antidepressive Agents, Second-Generation : administration & dosage
in
Chirality
volume
14
issue
4
pages
347 - 350
publisher
John Wiley & Sons
external identifiers
  • wos:000175043400013
  • pmid:11968077
  • scopus:0036226035
ISSN
1520-636X
DOI
10.1002/chir.10088
language
English
LU publication?
yes
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28cb06d2-45fd-4b58-8196-3e03276bd905 (old id 108451)
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http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11968077&dopt=Abstract
date added to LUP
2007-07-06 11:22:27
date last changed
2017-01-01 04:55:00
@article{28cb06d2-45fd-4b58-8196-3e03276bd905,
  abstract     = {Portacaval shunted (PCS) rats, a model of hepatic encephalopathy, and control animals were administered racemic venlafaxine for 14 days (10 mg/kg). The levels of the S- and R-enantiomers and the S/R-enantiomer ratios of venlafaxine and its metabolites were assessed by an enantiomer-selective chromatographic assay in serum, brain parenchyma, and brain dialysate of both groups. Higher levels of the S- and R-enantiomers of venlafaxine were found in serum and brain of PCS vs. normal rats (median values of S- and R-venlafaxine in serum: 290 and 201 nM in PCS; 97 and 66 nM in normal rats; median values of S- and R-venlafaxine in cortex: 956 and 939 nM in PCS; 357 and 318 nM in normal rats). Interestingly, similar S/R-venlafaxine ratios were observed in PCS and normal rats both in serum (S/R = 1.4) and brain compartments (S/R = l.0-1.1). These findings may have clinical relevance for the safety of venlafaxine in chronic hepatic encephalopathy.},
  author       = {Wikell, Cecilia and Eap, Chin B and Josefsson, Martin and Apelqvist, Gustav and Ahlner, Johan and Baumann, Pierre and Bengtsson, Finn},
  issn         = {1520-636X},
  keyword      = {Cyclohexanols : administration & dosage,Cyclohexanols : chemistry,Cyclohexanols : pharmacokinetics,Disease Models,Animal,Hepatic Encephalopathy : drug therapy,Hepatic Encephalopathy : metabolism,Human,Male,Portacaval Shunt,Rats,Surgical,Sprague-Dawley,Safety,Stereoisomerism,Brain : metabolism,Second-Generation : pharmacokinetics,Second-Generation : chemistry,Antidepressive Agents,Second-Generation : administration & dosage},
  language     = {eng},
  number       = {4},
  pages        = {347--350},
  publisher    = {John Wiley & Sons},
  series       = {Chirality},
  title        = {Disposition of venlafaxine enantiomers in rats with hepatic encephalopathy after chronic drug treatment.},
  url          = {http://dx.doi.org/10.1002/chir.10088},
  volume       = {14},
  year         = {2002},
}