Mutual inhibition between quinine and etoposide by human liver microsomes. Evidence for cytochrome P4503A4 involvement in their major metabolic pathways.

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Citation

Zhao XJ, Kawashiro T, Ishizaki T

Mutual inhibition between quinine and etoposide by human liver microsomes. Evidence for cytochrome P4503A4 involvement in their major metabolic pathways.

Drug Metab Dispos. 1998 Feb;26(2):188-91.

PubMed ID
9456308 [ View in PubMed
]
Abstract

The mutual inhibition between quinine and etoposide with their major metabolic pathways (i.e. quinine 3-hydroxylation and etoposide 3'-demethylation) was examined in vitro by human liver microsomes. Etoposide inhibited quinine 3-hydroxylation in a concentration-dependent manner with a mean IC50 of 65 microM. The mean maximum inhibition by etoposide (100 micro) of quinine 3-hydroxylation was about 60%. Similarly, etoposide 3'-demethylation was inhibited by quinine in a concentration-related manner with a mean IC50 value of 90 microM. The mean maximum inhibition by quinine (100 M) of etoposide 3'-demethylation was about 52%. An excellent correlation (r = 0.947, p < 0.01) between quinine 3-hydroxylase and etoposide 3'-demethylase activities in six different human liver microsomes was observed. Two inhibitors of CYP3A4, ketoconazole (1 microM) and troleandomycin (100 microM), inhibited quinine 3-hydroxylation by about 90% and 80%, and etoposide 3'-demethylation by about 75% and 65%, respectively. We conclude that quinine and etoposide mutually inhibit the metabolism of each other, consistent with the previous finding that CYP3A4 catalyzes the metabolism of both substrates.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Cytochrome P450 3A4P08684Details
Drug Interactions
DrugsInteraction
Acenocoumarol
Etoposide
The therapeutic efficacy of Acenocoumarol can be increased when used in combination with Etoposide.
Dicoumarol
Etoposide
The therapeutic efficacy of Dicoumarol can be increased when used in combination with Etoposide.
Fluindione
Etoposide
The therapeutic efficacy of Fluindione can be increased when used in combination with Etoposide.
Phenindione
Etoposide
The therapeutic efficacy of Phenindione can be increased when used in combination with Etoposide.
Phenprocoumon
Etoposide
The therapeutic efficacy of Phenprocoumon can be increased when used in combination with Etoposide.