The combination of diabetes and
hyperlipidemia promotes the development of
atherosclerosis. Therefore, it is important for diabetic patients to control blood fat. 3-Hydroxy-3-methylglutaryl
enzyme A (
HMG-CoA) reductase inhibitors (
statins), like
pravastatin, are frequently administered to diabetic patients for this purpose. Although the alterations of metabolic
enzymes and transporters in the diabetic liver maybe change the disposition of
pravastatin, the effect has not been fully investigated. In the present study, we investigated the disposition of
pravastatin and the
mRNA expression of transporters in the liver.
Pravastatin (5 mg.kg(-1)
body weight) was administered intravenously to diabetic rats, and the
pravastatin concentrations in the plasma, urine, and bile were measured by high-performance liquid chromatography. Changes in the
mRNA expressions of
multidrug resistance-associated protein 2 (MRP2) and organic
anion transporting
polypeptide 2 (OATP2) in the liver were also estimated using
reverse transcriptase-polymerase chain reaction (RT-PCR). We found that the plasma
pravastatin concentration was lower in the diabetic rat because the transportation of
pravastatin into hepatocytes was promoted along with increased expression of OATP2. The biliary excretion ratio of
pravastatin was significantly lower in the diabetic rat because the
pravastatin transportation into bile was reduced along with the decreased expression of MRP2. To clarify these phenomena, the analysis of
mRNA expression using real-time PCR and the measurement of the amount and the activity of
proteins are necessary in future study.