Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate.

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 (36,100 microg min/ml) was significantly greater and smaller than those in control rats (1040 microg min/ml) and rats with U-ARF (50,300 microg 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.