To identify the metabolite and CYP450 isoforms involved in rat liver microsomal metabolism of TM208. The present study investigated the metabolism of TM208 and the effects of selective CYP450 inhibitors on the metabol...To identify the metabolite and CYP450 isoforms involved in rat liver microsomal metabolism of TM208. The present study investigated the metabolism of TM208 and the effects of selective CYP450 inhibitors on the metabolism of TM208 in rat liver microsomes. Various specific inhibitors of CYP were used to identify the isoforms of CYP involved in the metabolism of TM208. The inhibitor of CYP2D and that of CYP2B had strong inhibitory effects on TM208 metabolism in a concentration-de- pendant manner, the inhibitor of CYP1A had a modest inhibitory effect, and the inhibitor of CYP3A seemed not to have an obvious inhibitory effect on TM208 metabolism. TM208 might mainly be metabolized by CYP2D and CYP2B in rat liver microsomes.展开更多
OBJECTIVE: To observe the significant differences in the frequencies of the cytochrome P450 2D6 (CYP2D6) alleles in Chinese popoulations. METHODS: Tetra-primer polymerase chain reaction (PCR), allele specific amplific...OBJECTIVE: To observe the significant differences in the frequencies of the cytochrome P450 2D6 (CYP2D6) alleles in Chinese popoulations. METHODS: Tetra-primer polymerase chain reaction (PCR), allele specific amplification (ASA) PCR and multiplex long PCR were developed to detect the CYP2D6 alleles * 2, * 3, * 4, * 5, * 6, * 8, * 10 and * 14 in 223 subjects from Chinese mainland. RESULTS: The CYP2D6 * 5 allele was the most frequent poor metabolizer (PM) allele in Chinese (7.2%), followed by CYP2D6 * 14 (2.0%) which was only detected in orientals. There was only 0.2% CYP2D6 * 4, and no CYP2D6 * 3, * 6 and * 8 were detected. In contrast to the Caucasians, the most frequent allele in Chinese was the * 10 allele with a frequency of 51.6%. CONCLUSION: The frequencies of PM alleles, CYP2D6 * 5 and CYP2D6 * 14, were higher; but the frequency of CYP2D6 * 10 was lower in mainland Chinese population than that in other orientals.展开更多
基金National Basic Research Program of China (863 Program,Grant No.2004AA2Z3783)National Natural Science Foundation of China (Grant No.20672009)
文摘To identify the metabolite and CYP450 isoforms involved in rat liver microsomal metabolism of TM208. The present study investigated the metabolism of TM208 and the effects of selective CYP450 inhibitors on the metabolism of TM208 in rat liver microsomes. Various specific inhibitors of CYP were used to identify the isoforms of CYP involved in the metabolism of TM208. The inhibitor of CYP2D and that of CYP2B had strong inhibitory effects on TM208 metabolism in a concentration-de- pendant manner, the inhibitor of CYP1A had a modest inhibitory effect, and the inhibitor of CYP3A seemed not to have an obvious inhibitory effect on TM208 metabolism. TM208 might mainly be metabolized by CYP2D and CYP2B in rat liver microsomes.
文摘OBJECTIVE: To observe the significant differences in the frequencies of the cytochrome P450 2D6 (CYP2D6) alleles in Chinese popoulations. METHODS: Tetra-primer polymerase chain reaction (PCR), allele specific amplification (ASA) PCR and multiplex long PCR were developed to detect the CYP2D6 alleles * 2, * 3, * 4, * 5, * 6, * 8, * 10 and * 14 in 223 subjects from Chinese mainland. RESULTS: The CYP2D6 * 5 allele was the most frequent poor metabolizer (PM) allele in Chinese (7.2%), followed by CYP2D6 * 14 (2.0%) which was only detected in orientals. There was only 0.2% CYP2D6 * 4, and no CYP2D6 * 3, * 6 and * 8 were detected. In contrast to the Caucasians, the most frequent allele in Chinese was the * 10 allele with a frequency of 51.6%. CONCLUSION: The frequencies of PM alleles, CYP2D6 * 5 and CYP2D6 * 14, were higher; but the frequency of CYP2D6 * 10 was lower in mainland Chinese population than that in other orientals.
