Effect of CYP3A1(23) induction on clarithromycin pharmacokinetics in rats with diabetes mellitus.
After intravenous and oral administration of clarithromycin at a dose of 20 mg/kg of body weight to rats with diabetes mellitus induced by alloxan (DMIA) and diabetes mellitus induced by streptozotocin (DMIS), the area under the curve values were significantly smaller than those of respective control rats. The in vitro intrinsic clearance values for the disappearance of clarithromycin were significantly faster in both rats with DMIA and rats with DMIS than in control rats. The above data suggested that metabolism of clarithromycin increased in both types of diabetic rat due to an increase in the expression and mRNA level of CYP3A1(23) in the rats.
Kim
Yu C
YC
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Gu, Seoul 151-742, South Korea.
Lee
Joo H
JH
Kim
So H
SH
Lee
Myung G
MG
D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis*; D017291:Clarithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D004790:Enzyme Induction; D051381:Rats; D013311:Streptozocin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D013311:Streptozocin; D000496:Alloxan; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A; D017291:Clarithromycin