Pharmacokinetic scaling of epirubicin using allometric and species-invariant time methods

• Published in: Journal of pharmaceutical investigation Vol. 45; no. 5; pp. 441 - 448
• Main Authors: Shin, Dae Hwan, Park, Seung Hyeok, Jeong, Sung Woo, Kwon, Oh-Seung, Park, Chun-Woong, Han, Kun, Chung, Youn Bok
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.10.2015; 한국약제학회
• Subjects: Biomedical and Life Sciences; Biomedicine; Research Article; 약학; Species-invariant time methods; Epirubicin; Clearance; Allometric scaling; Pharmacokinetics
• ISSN: 2093-5552; 2093-6214
• DOI: 10.1007/s40005-015-0189-9

The pharmacokinetics of epirubicin, an anthracycline, were investigated after intravenous bolus administration (5 mg/kg) in mice, rats, rabbits and dogs. Based on animal data, we predicted the following human pharmacokinetic parameters using allometric scaling: 120 and 35.2 L/h for total body clearance (CL t ) using simple and maximum life-span potential (MLP)-corrected allometry, respectively; 702 L for steady-state volume of distribution (V dss ). The scaled V dss value was twofold lower than the corresponding values in humans. However, the scaled CL t values were consistent with those clinically observed in humans (35.6–133.4 L/h). We also predicted human parameters using species-invariant time transformations (equivalent time, kallynochrons, apolysichrons and dienetichrons). The mean V dss (854 L) obtained using kallynochrons and that derived from simple allometry were comparable. The lowest CL t (121 L/h) derived using kallynochrons was comparable to that obtained using simple allometry. The results of this study also indicated that the predicted human CL t 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.