Pharmacokinetics of Liquiritigenin in Mice,Rats, Rabbits,and Dogs,and Animal Scale-Up |
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| Authors: | Hee E Kang Hye Y Jung Yu K Cho So H Kim Se I Sohn Seung R Baek Myung G Lee |
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| Institution: | 1. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea;2. Department of Pharmacology, College of Dentistry and Research Institute of Oral Science, Kangnung National University, Kangnung, South Korea;3. Daewon Pharmaceutical Company, Ltd., Seoul, South Korea |
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| Abstract: | Pharmacokinetics of liquiritigenin (LQ) and its two glucuronide metabolites, M1 and M2, in mice, rats, rabbits, and dogs and animal scale-up of the pharmacokinetic parameters of LQ were evaluated. After intravenous administration of LQ, the AUC (AUC0?t) values of LQ, M1, and M2 were proportional to LQ doses in all animals studied. Animal scale-up of some pharmacokinetic parameters of LQ was performed based on the parameters after its intravenous administration (20 mg/kg; in the linear pharmacokinetic range) to the four species. Linear relationships were obtained (r > 0.968) between log CL (or CL/fu) (L/h) and log species body weight (W) (kg) CL (or CL/fu) = 3.29 (34.0) W0.723 (0.789)] and log Vss (or Vss/fu) (L) and log W (kg) Vss (or Vss/fu) = 0.340 (3.52) W0.882 (0.948)]. Interspecies scale-up of plasma concentration–time data of LQ using apolysichron (complex Dedrick plots) resulted in similar profiles, and plasma concentration–time profile of humans were predicted using the well-fitted four animal data. Our results indicate that the LQ data obtained from laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters of LQ in humans. These parameters can serve as guidelines for better planning of clinical studies. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4327–4342, 2009 |
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