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• W2053461760 abstract "1. Glucuronidation is the major route of metabolism of dihydrocodeine (DHC) and accounts for 25-30% of an oral dose in urine. The kinetics of DHC-6-glucuronide formation in liver microsomes from five human donors and the effect of a number of potential inhibitor drugs were examined using a newly developed and validated HPLC assay. 2. The formation of DHC-6-glucuronide exhibited atypical kinetics that conformed to the Hill equation. The mean intrinsic dissociation constant (Ks) and maximum velocity (Vmax) values were 1566 micromol/L and 0.043 micromol/min per g, respectively. The Ks and Vmax values varied 1.5- and 3.5-fold, respectively. 3. Seven drugs were tested for inhibitory effects on DHC glucuronidation at low (50 micromol/L) and high (500 micromol/L) concentrations. At 50 micromol/L, only diclofenac produced greater than 50% inhibition, while at concentrations of 500 micromol/L inhibition was greater than 35% for diclofenac, amitriptyline, oxazepam, naproxen, chloramphenicol and probenecid, but not paracetamol. 4. The present study found little interindividual variation in the activity of human liver microsomes for glucuronidation of DHC. Comparison of the results from the inhibition studies with those reported previously for codeine and morphine suggest that the UDP-glucuronosyltransferase isoform UGT2B7 is involved in the glucuronidation of DHC." @default.
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• W2053461760 date "1998-03-01" @default.
• W2053461760 modified "2023-10-16" @default.
• W2053461760 title "GLUCURONIDATION OF DIHYDROCODEINE BY HUMAN LIVER MICROSOMES AND THE EFFECT OF INHIBITORS" @default.
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• W2053461760 doi "https://doi.org/10.1111/j.1440-1681.1998.t01-19-.x" @default.
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