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.
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.
Choi
Hye D
HD
College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Kang
Hee E
HE
Chung
Hye J
HJ
Bae
Soo K
SK
Shin
Karen N
KN
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001798:Blood Proteins / Q000378:metabolism; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003681:Dehydration / Q000378:metabolism; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014527:Uric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014868:Water Deprivation / Q000502:physiology*
D001798:Blood Proteins; D001993:Bronchodilator Agents; D014527:Uric Acid; D013806:Theophylline; C031274:1,3-dimethyluric acid