Abstract
It has been reported from our laboratories that expression of CYP2E1 significantly increased and decreased in rats with acute renal failure induced by uranyl nitrate (U-ARF) treated with recombinant human growth hormone (rGH) for one day (U-ARF1) compared with those in control rats and rats with U-ARF, respectively. Chlorzoxazone (CZX) primarily undergoes hydroxylation to form 6-hydroxychlorzoxazone (OH-CZX) catalyzed mainly by CYP2E1 in rats. Hence, the effects of rGH on the pharmacokinetics of intravenous CZX (20 mg/kg) were investigated in rats with U-ARF. Based on CYP2E1 expression, it could be expected that in rats with U-ARF1, the formation of OH-CZX significantly increased and decreased compared with those in control rats and rats with U-ARF, respectively. This was proven in the following results. First, the total area under the plasma concentration-time curve from time zero to 8 hr (AUC 0→8 hr) of OH-CZX in rats with U-ARF1 (36100 μg min/ml) was significantly greater and smaller than those in control rats (1040 μg min/ml) and rats with U-ARF (50300 μg min/ml), respectively. Second, the AUC 0→8 hr, OH-CZX/AUC CZX ratio in rats with U-ARF1 (28.9) was significantly greater and smaller than those in control rats (0.468) and rats with U-ARF (72.6), respectively.
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