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  • Title: Effects of water deprivation on the pharmacokinetics of theophylline and one of its metabolites, 1,3-dimethyluric acid, after intravenous and oral administration of aminophylline to rats.
    Author: Choi HD, Kang HE, Chung HJ, Bae SK, Shin KN, Lee MG.
    Journal: Biopharm Drug Dispos; 2007 Nov; 28(8):445-54. PubMed ID: 17847127.
    Abstract:
    It has been reported that the expressions of hepatic microsomal cytochrome P450 (CYP) 1A1/2, 2B1/2 and 3A1/2 were not changed in rats with water deprivation for 72 h (rat model of dehydration) compared with the controls. It has been also reported that 1,3-dimethyluric acid (1,3-DMU) was formed from theophylline via CYP1A1/2 in rats. Hence, it could be expected that the formation of 1,3-DMU could be comparable between the two groups of rats. As expected, after both intravenous and oral administration of theophylline at a dose of 5 mg/kg to the rat model of dehydration, the AUC of 1,3-DMU was comparable to the controls. After both intravenous and oral administration of theophylline to the rat model of dehydration, the Cl(r) of both theophylline and 1,3-DMU was significantly slower than the controls. This could be due to significantly smaller urinary excretions of both theophylline and 1,3-DMU since the AUC of both theophylline and 1,3-DMU were comparable between the two groups of rats. The smaller urinary excretion of both theophylline and 1,3-DMU could be due to urine flow rate-dependent timed-interval renal clearance of both theophylline and 1,3-DMU in rats.
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