Islam et al. (23) studied the effect of high-dose IFN-a2b (INTRON A) on the activities of CYP enzymes. Seventeen patients with high-risk melanoma received IFN-a2b IV at a dose of 20 MU/m2/day for 5 days/week for 4 weeks (induction phase) followed by SC administration of IFN-a2b at a dose of 10 MU/m2/day for 3 days/week for 48 weeks (maintenance phase). In vivo CYP enzyme activities were measured by administrating the "Pittsburgh mixture" (Table 3). The "five-drug mixture" was given orally simultaneously. The results of the study indicated that high-dose IFN-a2b had different degrees of effect on CYP enzymes. There was a 60% inhibition in CYP1A2 activity, whereas no effect on CYP2E1 activity was noted. Significant inhibition of 1A2 and 2D6 were noted immediately after the first IFN-a2b dose, whereas significant inhibition of CYP2C19 was found on day 26. CYP inhibition led to the side effects (fever and neurological toxicity) of IFN-a2b-treated patients.

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