PMID- 19226288
OWN - NLM
STAT- MEDLINE
DCOM- 20090720
LR  - 20211020
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 156
IP  - 6
DP  - 2009 Mar
TI  - Pharmacokinetics of oltipraz in diabetic rats with liver cirrhosis.
PG  - 1019-28
LID - 10.1111/j.1476-5381.2008.00105.x [doi]
AB  - BACKGROUND AND PURPOSE: The incidence of diabetes mellitus is increased in 
      patients with liver cirrhosis. Oltipraz is currently in trials to treat patients 
      with liver fibrosis and cirrhosis induced by chronic hepatitis types B and C and 
      is primarily metabolized via hepatic cytochrome P450 isozymes CYP1A1/2, 2B1/2, 
      2C11, 2D1 and 3A1/2 in rats. We have studied the influence of diabetes mellitus 
      on pharmacokinetics of oltipraz and on expression of hepatic, CYP1A, 2B1/2, 2C11, 
      2D and 3A in rats with experimental liver cirrhosis. EXPERIMENTAL APPROACH: 
      Oltipraz was given intravenously (10 mg x kg(-1)) or orally (30 mg x kg(-1)) to 
      rats with liver cirrhosis induced by N-dimethylnitrosamine (LC rats) or with 
      diabetes, induced by streptozotocin (DM rats) or to rats with both liver 
      cirrhosis and diabetes (LCD rats) and to control rats, and pharmacokinetic 
      variables measured. Protein expression of hepatic CYP1A, 2B1/2, 2C11, 2D and 3A 
      was measured using Western blot analysis. KEY RESULTS: After i.v. or p.o. 
      administration of oltipraz to LC and DM rats, the AUC was significantly greater 
      and smaller, respectively, than that in control rats. In LCD rats, the AUC was 
      that of LC and DM rats (partially restored towards control rats). Compared with 
      control rats, the protein expression of hepatic CYP1A increased, that of CYP2C11 
      and 3A decreased, but that of CYP2B1/2 and 2D was not altered in LCD rats. 
      CONCLUSIONS AND IMPLICATIONS: In rats with diabetes and liver cirrhosis, the AUC 
      of oltipraz was partially restored towards that of control rats.
FAU - Ahn, C Y
AU  - Ahn CY
AD  - College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul 
      National University, Seoul, South Korea.
FAU - Bae, S K
AU  - Bae SK
FAU - Bae, S H
AU  - Bae SH
FAU - Kim, T
AU  - Kim T
FAU - Jung, Y S
AU  - Jung YS
FAU - Kim, Y C
AU  - Kim YC
FAU - Lee, M G
AU  - Lee MG
FAU - Shin, W G
AU  - Shin WG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Pyrazines)
RN  - 0 (Schistosomicides)
RN  - 0 (Thiones)
RN  - 0 (Thiophenes)
RN  - 6N510JUL1Y (oltipraz)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Animals
MH  - Area Under Curve
MH  - Cytochrome P-450 Enzyme System/biosynthesis
MH  - Diabetes Mellitus, Experimental/complications/*metabolism
MH  - Liver/enzymology
MH  - Liver Cirrhosis, Experimental/complications/*metabolism
MH  - Pyrazines/*pharmacokinetics
MH  - Rats
MH  - Schistosomicides/*pharmacokinetics
MH  - Thiones
MH  - Thiophenes
PMC - PMC2697721
EDAT- 2009/02/20 09:00
MHDA- 2009/07/21 09:00
PMCR- 2010/03/01
CRDT- 2009/02/20 09:00
PHST- 2009/02/20 09:00 [entrez]
PHST- 2009/02/20 09:00 [pubmed]
PHST- 2009/07/21 09:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - BPH105 [pii]
AID - 10.1111/j.1476-5381.2008.00105.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2009 Mar;156(6):1019-28. doi: 10.1111/j.1476-5381.2008.00105.x.