title: Interspecies scaling of oleanolic acid in mice, rats, rabbits and dogs and prediction of human pharmacokinetics.
abstract: This study was conducted to predict the pharmacokinetics of oleanolic acid in humans based on animal data by allometry and several species-invariant time methods. Oleanolic acid was injected intravenously to mice, rats, rabbit and dogs (dose 1 mg/kg). The serum concentration-time profiles of oleanolic acid were best described by bi-exponential equation in all animal species. The average Cl, V ( ss ) and t ( 1/2 ) were 0.065 L/h, 0.019 L and 28.7 min in mice, 0.47 +/- 0.06 L/h, 0.117 +/- 0.029 L and 29.7 +/- 12.2 min in rats, 2.77 +/- 0.88 L/h, 1.83 +/- 0.60 L and 84.4 +/- 16.9 min in rabbits and 14.0 +/- 0.7 L/h, 9.2 +/- 10.1 L and 54.5 +/- 57.2 min in dogs, respectively. Based on animal data, human pharmacokinetic parameters of Cl, V ( ss ) and t (1/2) were predicted by simple allometry. In addition, actual concentration-time profiles obtained from animals were transformed to human profiles by species-invariant times of kallynochron, apolysichron and dienetichron. The predicted human pharmacokinetic parameters of Cl, V ( ss ) and t (1/2) by using simple allometry and species-invariant time transformation method ranged from 48.3-97.2 L/h, 49.1-92.9 L and 45.6-187.2 min, respectively. Those predicted parameters of oleanolic acid may be useful in designing dosing schedules of oleanolic acid in future clinical studies.
authors.affiliation: Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Ji
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Jeong
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Park
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Park
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D004285:Dogs; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008813:Mice, Inbred ICR; D008954:Models, Biological; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011237:Predictive Value of Tests; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
chemical_list: D009828:Oleanolic Acid