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

Hye D. Choi; Hee E. Kang; Hye J. Chung; Soo K. Bae; Karen N. Shin; Myung G. Lee

doi:10.1002/bdd.573

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

Hye D. Choi, Hee E. Kang, Hye J. Chung, Soo K. Bae, Karen N. Shin, Myung G. Lee

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 72h (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 5mg/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.

Original language	English
Pages (from-to)	445-454
Number of pages	10
Journal	Biopharmaceutics and Drug Disposition
Volume	28
Issue number	8
DOIs	https://doi.org/10.1002/bdd.573
State	Published - Nov 2007

Keywords

1,3-DMU
CYP1A1/2,2B1/2 and 3A1/2
Pharmacokinetics
Rats
Theophylline
Water deprivation for 72 h

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10.1002/bdd.573

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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",

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 72h (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 5mg/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 Clr 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.",

keywords = "1,3-DMU, CYP1A1/2,2B1/2 and 3A1/2, Pharmacokinetics, Rats, Theophylline, Water deprivation for 72 h",

author = "Choi, {Hye D.} and Kang, {Hee E.} and Chung, {Hye J.} and Bae, {Soo K.} and Shin, {Karen N.} and Lee, {Myung G.}",

year = "2007",

month = nov,

doi = "10.1002/bdd.573",

language = "English",

volume = "28",

pages = "445--454",

journal = "Biopharmaceutics and Drug Disposition",

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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. / Choi, Hye D.; Kang, Hee E.; Chung, Hye J. et al.
In: Biopharmaceutics and Drug Disposition, Vol. 28, No. 8, 11.2007, p. 445-454.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Choi, Hye D.

AU - Kang, Hee E.

AU - Chung, Hye J.

AU - Bae, Soo K.

AU - Shin, Karen N.

AU - Lee, Myung G.

PY - 2007/11

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N2 - 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 72h (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 5mg/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 Clr 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.

AB - 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 72h (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 5mg/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 Clr 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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KW - CYP1A1/2,2B1/2 and 3A1/2

KW - Pharmacokinetics

KW - Rats

KW - Theophylline

KW - Water deprivation for 72 h

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VL - 28

SP - 445

EP - 454

JO - Biopharmaceutics and Drug Disposition

JF - Biopharmaceutics and Drug Disposition

IS - 8

ER -

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

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Keywords

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