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Disposition of venlafaxine enantiomers in rats with hepatic encephalopathy after chronic drug treatment
Author(s) -
Wikell Cecilia,
Eap Chin B.,
Josefsson Martin,
Apelqvist Gustav,
Ahlner Johan,
Baumann Pierre,
Bengtsson Finn
Publication year - 2002
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.10088
Subject(s) - venlafaxine , chemistry , enantiomer , portacaval shunt , pharmacokinetics , hepatic encephalopathy , pharmacology , medicine , endocrinology , antidepressant , cirrhosis , hippocampus , stereochemistry , portal hypertension
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. Chirality 14:347–350, 2002. © 2002 Wiley‐Liss, Inc.