Pharmacokinetics of liquiritigenin in mice, rats, rabbits, and dogs, and animal scale-up.
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 (AUC(0-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/f(u)) (L/h) and log species body weight (W) (kg) [CL (or CL/f(u)) = 3.29 (34.0) W(0.723 (0.789))] and log V(ss) (or V(ss)/f(u)) (L) and log W (kg) [V(ss) (or V(ss)/f(u)) = 0.340 (3.52) W(0.882 (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.
Kang
Hee E
HE
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
Jung
Hye Y
HY
Cho
Yu K
YK
Kim
So H
SH
Sohn
Se I
SI
Baek
Seung R
SR
Lee
Myung G
MG
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001835:Body Weight; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D044950:Flavanones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008813:Mice, Inbred ICR; D011237:Predictive Value of Tests; D011485:Protein Binding; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D044950:Flavanones; C083152:liquiritigenin