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Hepatotoxicity of citalopram in
rats and first-pass metabolism.
Fredricson Overo K,
Svendsen O.
A chronic oral toxicity study of citalopram in
rats revealed dose dependent hepatic fatty infiltrations in male rats
while female rats were unaffected. Subsequent studies demonstrated
markedly reduced availability due to first-pass hepatic metabolism in
male rats and roughly complete availability in females. Pretreatment of
male rats with phenobarbital for 2 weeks caused increased metabolism and
simultaneous administration of phenobarbital and citalopram gave more
pronounced fatty infiltrations than citalopram alone. A connection is
suggested between the first-pass metabolism in male rats and the
hepatotoxicity, which is possibly mediated through a metabolite or
intermediate formed in toxic amount during the first passage of the
liver.
PMID: 277099 [PubMed - indexed for MEDLINE]
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