British journal of clinical pharmacology
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Br J Clin Pharmacol · May 2012
Randomized Controlled TrialAssessment of the pharmacology and tolerability of PF-04457845, an irreversible inhibitor of fatty acid amide hydrolase-1, in healthy subjects.
AIMS To evaluate the pharmacology and tolerability of PF-04457845, an orally available fatty acid amide hydrolase-1 (FAAH1) inhibitor, in healthy subjects. ⋯ PF-04457845 was well tolerated at doses exceeding those required for maximal inhibition of FAAH1 activity and elevation of fatty acid amides.
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Br J Clin Pharmacol · May 2012
Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects.
To compare the O-demethylation (CYP2D6-mediated), N-demethylation (CYP3A4-mediated) and 6-glucuronidation (UGT2B4/7-mediated) metabolism of codeine between methadone- and buprenorphine-maintained CYP2D6 extensive metabolizer subjects. ⋯ Methadone is associated with inhibition of CYP2D6 and UGTs 2B4 and 2B7 reactions in vivo, even though it is not a substrate for these enzymes. Plasma morphine was not altered, owing to the opposing effects of inhibition of both formation and elimination; however, morphine-6-glucuronide (analgesically active) concentrations were substantially reduced. Drug interactions with methadone are likely to include drugs metabolized by various UGTs and CYP2D6.
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Br J Clin Pharmacol · May 2012
Biography Historical ArticleDavid Grahame Grahame-Smith: clinical pharmacologist. 1933-2011.