title: Effects of recombinant human growth hormone on the pharmacokinetics of intravenous chlorzoxazone in rats with acute renal failure induced by uranyl nitrate.
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.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, South Korea.
authors.forename: Won- Suk
authors.initials: W
authors.lastname: Chung
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Kim
authors.forename: Inchul
authors.initials: I
authors.lastname: Lee
authors.forename: Sang Geon
authors.initials: SG
authors.lastname: Kim
authors.forename: Myung Gull
authors.initials: MG
authors.lastname: Lee
authors.forename: So Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D002384:Catalysis; D002753:Chlorzoxazone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004790:Enzyme Induction; D019382:Human Growth Hormone / Q000494:pharmacology*; D006801:Humans; D006900:Hydroxylation; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology*; D014502:Uranyl Nitrate
chemical_list: D001798:Blood Proteins; D011994:Recombinant Proteins; D014502:Uranyl Nitrate; D019382:Human Growth Hormone; C039289:6-hydroxychlorzoxazone; D019392:Cytochrome P-450 CYP2E1; D002753:Chlorzoxazone