Interspecies scaling of oleanolic acid in mice, rats, rabbits and dogs and prediction of human pharmacokinetics.
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.
Ji
Hye Young
HY
Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan 570-749, Korea.
Shin
Beom Soo
BS
Jeong
Dong Won
DW
Park
Eun Jeong
EJ
Park
Eun-Seok
ES
Yoo
Sun Dong
SD
Lee
Hye Suk
HS
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
D009828:Oleanolic Acid