RT Journal Article SR Electronic T1 Mutual Inhibition between Quinine and Etoposide by Human Liver Microsomes JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 188 OP 191 VO 26 IS 2 A1 Xue-Jun Zhao A1 Takashi Kawashiro A1 Takashi Ishizaki YR 1998 UL http://dmd.aspetjournals.org/content/26/2/188.abstract AB 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 IC50of 65 μM. The mean maximum inhibition by etoposide (100 μM) 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 μM. 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 μM) and troleandomycin (100 μM), 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. The American Society for Pharmacology and Experimental Therapeutics