Becquemont et al. (21) studied the effect of IFN-a and ribavirin combination therapy on the activities of CYP1A2, CYP2D6, CYP3A4, and N-acetyltransferase-2 (NAT2) after one month of treatment. There were 14 patients with chronic hepatitis C in the study. The patients received three MU of IFN-a three times a week and 600 mg ribavirin twice a day in five patients and 500 mg ribavirin twice a day in nine patients (who were less than 75 kg of body weight). Before the initiation of the therapy, the patients also received 80 mg dextromethorphan and 140 mg caffeine. The results of this study are summarized below:
■ CYP3A4 activity increased almost by threefold just before treatment to one month of IFN-a and ribavirin therapy. However, the increase in CYP3A4 activity was not unidirectional. There were seven patients in whom CYP3A4 activity increased from 112% to 1677%, whereas in six patients, CYP3A4 activity decreased by 47% to 67% from pretreatment values.
■ CYP2D6 activity also increased almost by threefold, but, like CYP3A4 activity, the increase was not unidirectional. CYP2D6 activity increased from 120% to 322% in nine patients and decreased from 42% to 93% in five patients.
■ CYP1A2 and NAT2 activities remained unchanged from the pretreatment period to one month after treatment. Smoking status did not alter CYP1A2 activity before and after treatment.
Overall, the study indicates that IFN-a and ribavirin combination therapy can decrease or increase the activities of CYP3A4 and CYP2D6 in patients with chronic hepatitis C. Therefore, individual therapeutic drug monitoring may become necessary in this patient population if they are taking any drug that is a substrate for either CYP3A4 or CYP2D6.
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