Pharmacokinetics of theophylline in diabetes mellitus rats: induction of CYP1A2 and CYP2E1 on 1,3-dimethyluric acid formation.

Article Details

Citation

Copy to clipboard

Kim YC, Lee AK, Lee JH, Lee I, Lee DC, Kim SH, Kim SG, Lee MG

Pharmacokinetics of theophylline in diabetes mellitus rats: induction of CYP1A2 and CYP2E1 on 1,3-dimethyluric acid formation.

Eur J Pharm Sci. 2005 Sep;26(1):114-23. doi: 10.1016/j.ejps.2005.05.004.

PubMed ID

15985363 [ View in PubMed

]

Abstract

Pharmacokinetic parameters of theophylline and one of its metabolites, 1,3-dimethyluric acid (1,3-DMU), were compared after intravenous and oral administration of aminophylline, 5mg/kg as theophylline, to diabetes mellitus rats induced by alloxan (DMIA) or streptozotocin (DMIS), and their respective control rats. In DMIA and DMIS rats, expression of CYP1A2 and 2E1 increased approximately three times. Theophylline was metabolized to 1,3-DMU by CYP1A2 and 2E1 in rats. Hence, it was expected that formation of 1,3-DMU increased in DMIA or DMIS rats. This was proven by the following results. First, after intravenous administration of theophylline, the AUC of 1,3-DMU was significantly greater in DMIA (110% increase) or DMIS (47.4% increase) rats. Second, the AUC of theophylline was significantly smaller in DMIA (26.1% decrease) or DMIS (30.1% decrease) rats because of significantly faster time-averaged total body clearance in DMIA (34.8% increase) or DMIS (42.7% increase) rats. Third, based on in vitro hepatic microsomal studies, intrinsic 1,3-DMU formation clearances were significantly faster in DMIA (20.4% increase) or DMIS (30.7% increase) rats than respective control rats. Similar results (AUC values of theophylline and 1,3-DMU) were also obtained after oral administration.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Theophylline	Cytochrome P450 2E1	Protein	Humans	Unknown	Substrate	Details