0 119

Cited 57 times in

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

Authors
 Yu Chul Kim  ;  Ae Kyung Lee  ;  Joo Hyun Lee  ;  Inchul Lee  ;  Duk Chul Lee  ;  So Hee Kim  ;  Sang Geon Kim  ;  Myung Gull Lee 
Citation
 EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, Vol.26(1) : 114-123, 2005 
Journal Title
 EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES 
ISSN
 0928-0987 
Issue Date
2005
MeSH
Administration, Oral ; Alloxan ; Aminophylline/administration & dosage ; Aminophylline/pharmacokinetics ; Animals ; Cytochrome P-450 CYP1A2/biosynthesis* ; Cytochrome P-450 CYP1A2/genetics ; Cytochrome P-450 CYP2E1/biosynthesis* ; Cytochrome P-450 CYP2E1/genetics ; Diabetes Mellitus, Experimental/chemically induced ; Diabetes Mellitus, Experimental/metabolism* ; Enzyme Induction ; Injections, Intravenous ; Male ; RNA, Messenger/analysis ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Theophylline/blood ; Theophylline/pharmacokinetics* ; Uric Acid/analogs & derivatives* ; Uric Acid/blood ; Uric Acid/pharmacokinetics
Keywords
Theophylline ; 1,3-DMU ; CYP1A2 ; CYP2E1 ; Pharmacokinetics ; Diabetes mellitus ; Alloxan ; Streptozotocin ; Rats
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, 5 mg/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.
Full Text
http://www.sciencedirect.com/science/article/pii/S0928098705001703
DOI
10.1016/j.ejps.2005.05.004
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Family Medicine (가정의학교실) > 1. Journal Papers
Yonsei Authors
Lee, Duk Chul(이덕철) ORCID logo https://orcid.org/0000-0001-9166-1813
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/151090
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links