Pharmacokinetic Changes of Tolbutamide After Oral Administration to Rabbits with Alloxan-Induced Diabetes Mellitus

알록산으로 유도된 당뇨병 가토에 톨부타마이드 경구투여시 약물동태변화

The changes in pharmacokinetic parameters of tolbutamide, such as the area under the plasma concentration-time curve from time zero to time infinity (AUC) and elimination rate constant (Kel) were evaluated after oral administration of the drug to rabbits with acute and chronic alloxan-induced diabetes mellitus (AIDRs). After oral administration, the plasma concentrations of tolbutamide were significantly higher between 9 and 12 hr in chronic AIDRs compared with these in control rabbits. Therefore, the AUC was significantly greater in chronic AIDRs $(3,490{\pm}649\;versus\;5,020{\pm}1,030{\mu}gml{\cdot}hr)$. This could be due to inhibition of tolbutamide metabolism by liver in AIDRs since tolbutamide is essentially completely metabolized in liver. Impaired liver and kidney function in AIDRs were based on blood chemistry and tissue microscopy. The absorption rate constant and Kel were significantly slower in chronic AIDRs compared with those in control rabbits.