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KMID : 0043320090320020251
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Archives of Pharmacal Research
2009 Volume.32 No. 2 p.251 ~ p.257
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Interspecies Scaling of Oleanolic Acid in Mice, Rats, Rabbits and Dogs and Prediction of Human Pharmacokinetics
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Lee Hye-Suk
Ji Hye-Young
Shin Beom-Soo
Yoo Sun-Dong
Park Eun-Seok
Jeong Dong-Won
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Abstract
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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, Vss and t1/2 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, Vss and t1/2 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, Vss and t1/2 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.
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KEYWORD
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Oleanolic acid, Allometry, Species-invariant time method
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