Prediction of Human Pharmacokinetic Parameters Using Animal Data and Principles of Allometry

Abstract

Allometry scaling of preclinical pharmacokinetic parameters for bicifadine (CAS 71195-57-8), a novel non-narcotic analgesic, was performed to predict the human pharmacokinetic parameters of clearance (CL_iv and CL_oral) and volume of distribution (V_z). The metabolism pattern, biotransformation pathways, and the predominant urinary excretion of the formed metabolites of bicifadine were found to be similar amongst mice, rats, monkeys and humans facilitating the scaling process. The availability of gender specific data in the preclinical species rendered the prediction of bicifadine parameters in gender specific groups. The human parameters for CL_iv,V_z, and CL_oral were predicted by allometric equations: 1.5252W^0.742 (R² = 0.9989), 1.3489W^0.8484 (R² = 0.9896), 3.2516W^0.7694 (R² = 0.9875), respectively. The absolute bioavailability for bicifadine was estimated to be approximately 67%. The predicted CL_oral (95 L/h) was within 45% of the human reported value (59 L/h). Overall, based on the closeness of allometric exponents (within 15% of suggested values), simple allometry approach could be used to prospectively predict the human pharmacokinetic parameters of bicifadine with confidence.

Key words

Allometiy - Bicafadine, clearance, pharmacokinetics, volume of distribution - CAS 71195-57-8 - Non-narcotic analgesic

• Literature

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