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Adverse reaction to intravenous gadoteridol 总被引:1,自引:0,他引:1
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Kyoung-Ah Kim Min-Jung Kim Ji-Young Park Ji-Hong Shon Young-Ran Yoon Sang-Seop Lee Kwang-Hyeon Liu Jin-Ho Chun Myung-Ho Hyun Jae-Gook Shin 《Drug metabolism and disposition》2003,31(10):1227-1234
The stereoselective metabolism of lansoprazole enantiomers was evaluated by incubation of human liver microsomes and cDNA-expressed cytochrome p450 (p450) enzymes to understand and predict their stereoselective disposition in humans in vivo. The intrinsic clearances (Clint) of the formation of both hydroxy and sulfone metabolites from S-lansoprazole were 4.9- and 2.4-fold higher than those from the R-form, respectively. The sums of formation Clint of both metabolites were 13.5 and 57.3 microl/min/mg protein for R- and S-lansoprazole, respectively, suggesting that S-lansoprazole would be cleared more rapidly than the R-form. The p450 isoform selective inhibition study in liver microsomes, and the incubation study of cDNA-expressed enzymes, demonstrated that the stereoselective sulfoxidation is mediated by CYP3A4 and that the hydroxylation is mediated by CYP2C9 and CYP3A4 as well as by CYP2C19. Total Clint values of hydroxy and sulfone metabolite formation catalyzed by all these p450 enzymes were consistently higher for S-lansoprazole than for the R-form. The CYP3A4 produced the greatest difference of Clint between S- and R-enantiomers, mainly due to a difference of sulfoxidation metabolism (Clint 76.5 versus 10.8 microl/min/nmol of p450, respectively), whereas CYP2C19-catalyzed hydroxylation resulted in a minor difference of Clint between S- and R-enantiomers (179.6 versus 143.3 microl/min/nmol of p450, respectively). However, the affinity of CYP2C19 on hydroxylation was 5.7-fold higher for S-enantiomer than for the R-form (Km 2.3 versus 13.1 microM), suggesting that the role of CYP2C19 on stereoselective hydroxylation would be more prominent at concentrations around the usual therapeutic level. These findings suggest that both CYP2C19 and CYP3A4 are major enzymes contributing to the stereoselective disposition of lansoprazole, but stereoselective hydroxylation of lansoprazole enantiomers is mainly influenced by CYP2C19, especially at the usual therapeutic doses. 相似文献
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Intestinal schistosomiasis japonica: CT-pathologic correlation 总被引:1,自引:0,他引:1
Lee RC; Chiang JH; Chou YH; Rubesin SE; Wu HP; Jeng WC; Hsu CC; Tiu CM; Chang T 《Radiology》1994,193(2):539
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