Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate.
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| 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 (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.
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| Authors | Won- Suk Chung, Eun Jung Kim, Inchul Lee, Sang Geon Kim, Myung Gull Lee, So Hee Kim |
| Journal | Life sciences (Life Sci) Vol. 73 Issue 3 Pg. 253-63 (Jun 06 2003) ISSN: 0024-3205 [Print] Netherlands |
| PMID | 12757833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
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