Coexistence of Breast and Prostate Cancers in a 79-Year-Old Man

Abstract

e71 (HLM) and intestinal microsomes (HIM). The effects of relevant polymorphisms in UGT genes on the pharmacokinetics of clopidogrel were evaluated in 106 healthy volunteers. Results: UGT2B17 and UGT2B7 exhibited the highest activities for clopidogrel carboxylic acid glucuronidation, while UGT1A9, UGT1A3 and UGT2B4 showed lower activity. The K m for UGT2B7 and UGT2B17 were 21 and 181 µM, respectively, with respective V max of 51 and 511 pmol/min/mg and CL int,u of 2.4 and 2.8 µL/min/mg. In inhibition studies, the UGT2B7 and UGT1A9 inhibitor mefenamic acid inhibited clopidogrel acyl-β-D-glucuronide formation in HLM by 38%, and the UGT2B17 inhibitor imatinib inhibited clopidogrel glucuronidation in HIM by 85%. In healthy volunteers, UGT2B17 deletion was associated with a 10% decrease per allele in the clopidogrel acyl-β-D-glucuronide to clopidogrel carboxylic acid AUC ratio in plasma. Conclusions: It can be extrapolated from the in vitro results and the clinical data that UGT2B7 and UGT2B17 are the main enzymes involved in clopidogrel acyl-β-D-glucuronide formation in the liver and in the intestinal wall, respectively. Thus, UGT2B7 is probably the most important UGT form involved in the bioactivation of clopidogrel carboxylic acid to the acyl-β-D-glucuronide metabolite, leading to inactivation of the CYP2C8 enzyme.