Dose-Dependent Pharmacokinetics of Glycyrrhizin in Rats
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概要
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The dose-dependent pharmacokinetics of glycyrrhizin (GLZ) was investigated by measuring drug disappearance from plasma and biliary excretion in rats. The decline in plasma concentration was biexponential after an i.v. dose of 5,10,20,or 50 mg/kg. Dosage, however, had a marked effect on the pharmacokinetics, with a greater-than-proportional increase in area under the plasma concentration curve (AUC) at doses of 20 and 50 mg/kg, even though the increase was proportional at doses of 5 and 10 mg/kg. There was also a significant increase of the steady-state distribution volume (Vd_<ss>), as well as significant decreases in total body (CL_<tot>) and biliary (CL_B) clearances, at 20 and 50 mg/kg from those at 5-10 and 5-20 mg/kg, respectively. The AUC, Vd_<ss>, and renal clearance (CL_R) at a given dose showed no significant difference between rats with and without bile fistulas. The plasma unbound fraction (f_p) (0.006-0.026) increased with increasing plasma GLZ concentration over the observed range (2-900 μg/ml). No significant change in Vd_<ss> for unbound GLZ was observed between the doses, indicating that the distribution of GLZ into tissues is not changed by an increase in dose. On the other hand, a dose dependency in CL_<tot> for unbound GLZ was observed and confirmed to be attributed to dose dependency in CL_B for unbound GLZ since there was no significant difference in CL_R or metabolic clearance for unbound GLZ between the doses. The biliary excretion rates (V_B) at steady-state plasma unbound levels fitted reasonably well a Michaelis-Menten type equation with a maximum V_B of 98.77 μg/min and a Michaelis constant of 1.83 μg/ml. It was suggested that the saturable V_B may result in the dose dependence of CL_B. Thus, the pharmacokinetics of GLZ in rats is dose-dependent.
- 社団法人日本薬学会の論文
- 1992-07-25
著者
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石田 志朗
Faculty Of Pharmaceutical Sciences Tokushima Bunri University
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平良 全栄
Faculty of Pharmaceutical Sciences, Tokushima Bunri University
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崎谷 陽子
Faculty of Pharmaceutical Sciences, Tokushima Bunri University
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市川 勤
Faculty of Pharmaceutical Sciences, Tokushima Bunri University
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市川 勤
徳島文理大学薬学部医療薬学講座
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市川 勤
東北薬科大学
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平良 全栄
Faculty Of Pharmaceutical Sciences Tokushima Bunri University
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Sakiya Y
Tokushima Bunri Univ. Tokushima Jpn
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崎谷 陽子
Faculty Of Pharmaceutical Sciences Tokushima Bunri University
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崎谷 陽子
Faculty Of Pharmaceutical Science Tokushima University Of Arts And Science
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