Interspecies scaling of oleanolic acid in mice,rats, rabbits and dogs and prediction of human pharmacokinetics |
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Authors: | Hye Young Ji Beom Soo Shin Dong Won Jeong Eun Jeong Park Eun-Seok Park Sun Dong Yoo Hye Suk Lee |
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Affiliation: | (1) Drug Metabolism & Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Iksan, 570-749, Korea;(2) College of Pharmacy, Catholic University of Daegu, Gyeongsan, 712-202, Korea;(3) College of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Korea;(4) Drug Metabolism and Bioanalysis Laboratory, College of Pharmacy, Wonkwang University, Shinyongdong, Iksan, 570-749, Korea |
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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 contributed equally to this work. |
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Keywords: | Oleanolic acid Allometry Species-invariant time method |
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