Role of human cytochrome P450 3A4 in the metabolism of DA-8159, a new erectogenic.

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Ji HY, Lee HW, Kim HH, Kim DS, Yoo M, Kim WB, Lee HS

Role of human cytochrome P450 3A4 in the metabolism of DA-8159, a new erectogenic.

Xenobiotica. 2004 Nov-Dec;34(11-12):973-82.

PubMed ID

15801542 [ View in PubMed

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Abstract

The purpose of this paper was to characterize cytochrome P450 (CYP) enzymes involved in N-dealkylation of a new oral erectogenic, DA-8159 to DA-8164, a major circulating active metabolite, in human liver microsomes and to investigate the inhibitory potential of DA-8159 on CYP enzymes. CYP3A4 was identified as the major enzyme responsible for DA-8159 N-dealkylation to DA-8164 based on correlation analysis and specific CYP inhibitor and antibody-mediated inhibition study in human liver microsomes, and DA-8159 metabolism in cDNA expressed CYP enzymes. There is the possibility of drug-drug interactions when prescribing DA-8159 concomitantly with known inhibitors or inducers of CYP3A4. DA-8159 was found to be only a very weak inhibitor of eight major CYPs (1A2, 2A6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4), the largest inhibition occurring against CYP2D6 (IC5o 67.7 microM) in human liver microsomes. Drug-drug interactions would not be predicted on the basis of DA-8159 inhibiting the metabolism of coadministered drugs.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Udenafil	Cytochrome P450 3A4	Protein	Humans	Unknown	Substrate	Details