甘草酸與甘草次酸於兔體內之動力學比較   全文下載

Comparison of Pharmacokinetics between Glycyrrhizin and Glycyrrhetic Acid in Rabbits

甘草酸為一具生物活性之天然配醣體，甘草次酸為其非醣體及活性代謝物。甘草次酸之抗炎活性較甘草酸為強，亦為副作用醛類脂醇過多症之主因，本研究之目的為比較家兔口服等莫耳之甘草酸與甘草次酸後，其甘草次酸藥物動力學之差異。六隻紐西蘭大白兔以隨機交叉設計，口服給予178.5 μmol kg-1之甘草酸或甘草次酸後，以高效液相層析法測定血中甘草酸與甘草次酸之濃度；採用非室性模式計算動力學參數並用paired Student’s t-test 比較其統計上之差異。結果顯示口服甘草酸時，除了先有甘草酸原形於小腸吸收外，其代謝物甘草次酸的曲線下面積及平均滯留時間與口服甘草次酸相比較，顯著增加了443%及354%。因此，甘草酸可視為甘草次酸之極佳前驅藥。

Glycyrrhizin is a bioactive natural glycoside. Glycyrrhetic acid is an aglycone and an active metabolite of glycyrrhizin. The antiinflammatory activity of glycyrrhetic acid is even stronger than that of glycyrrhizin and glycyrrhetic acid is responsible for the adverse effect of aldosteronism. This study attempted to compare the pharmacokinetics of glycyrrhetic acid after oral administration of equal molar doses of glycyrrhizin and glycyrrhetic acid to rabbits. Six New Zealand White rabbits were orally given glycyrrhizin or glycyrrhetic acid at a dose of 178.5 μmol kg-1 in a randomized crossover design. HPLC methods were used to determine the serum concentrations of glycyrrhizin and glycyrrhetic acid. A noncompartment model was used to calculate the pharmacokinetic parameters and a paired Student’s t-test was used for statistical comparison. The results indicated that in addition to the absorption of glycyrrhizin per se at small intestine, oral dosing of glycyrrhizin resulted in higher AUC0-t and MRT of glycyrrhetic acid by 443 % and 354 %, respectively, than those after oral dosing of glycyrrhetic acid. It can be concluded that glycyrrhizin is a good prodrug of glycyrrhetic acid. 甘草酸為一具生物活性之天然配醣體，甘草次酸為其非醣體及活性代謝物。甘草次酸之抗炎活性較甘草酸為強，亦為副作用醛類脂醇過多症之主因，本研究之目的為比較家兔口服等莫耳之甘草酸與甘草次酸後，其甘草次酸藥物動力學之差異。六隻紐西蘭大白兔以隨機交叉設計，口服給予178.5 μmol kg-1之甘草酸或甘草次酸後，以高效液相層析法測定血中甘草酸與甘草次酸之濃度；採用非室性模式計算動力學參數並用paired Student’s t-test 比較其統計上之差異。結果顯示口服甘草酸時，除了先有甘草酸原形於小腸吸收外，其代謝物甘草次酸的曲線下面積及平均滯留時間與口服甘草次酸相比較，顯著增加了443%及354%。因此，甘草酸可視為甘草次酸之極佳前驅藥。