Interspecies pharmacokinetic scaling of 11-hydroxyaclanomycin X based on animal data

서지정보

ㆍ발행기관 : 충북대학교 동물의학연구소 ㆍ수록지정보 : Journal of Biomedical and Translational Research / 18권 / 1호
ㆍ저자명 : DaeHwanShin, So-YoungLee, SungWooJeong, Chun-WoongPark, YounBokChung

영어 초록

The pharmacokinetics of 11-Hydroxyaclacinomycin X (HAMX), a novel anthracycline, were investigated after intravenous bolus administration in mice, rats, rabbits and dogs. Based on animal data, we predicted the following human pharmacokinetic parameters using allometric scaling: 24.1 and 6.99 mL/min/kg for total body clearance (CLt) using simple and maximum life-span potential (MLP)-corrected allometry, respectively; 5.72 L/kg for steady-state volume of distribution (Vdss ). The corresponding allometric equation were CLt = 45.896W0.8452, CLt MLP = 31.175W1.1405 and Vdss = 10140x0.8653. These allometric equations were extrapolated to predict CLt and Vdss in human based on 70 kg body weight. We also predicted human parameters using species-invariant time transformations (equivalent time, kallynochrons, apolysichrons and dienetichrons). The values of Vdss (15.4-19.4 L/kg) obtained using invariant time transformations were larger than those obtained using simple allometry. However, the lowest CLt (17.0 mL/min/kg) derived usi ngdienetichrons was comparable to that obtained using simple allometry. The results of this study also indicated that the predicted human CLt generated using MLP-corrected allometry can be used for the selection of a safe dose for studies in healthy adult human volunteers. These results suggest that such approaches may be useful in designing pharmacokinetic studies for novel anthracyclines. The preliminary parameter values may be useful in designing early pharmacokinetic studies of HAMX in humans. The results could also be used to determine the safe dose for the therapeutics in various animals.

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