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Arzneimittelforschung 2009; 59(12): 625-630
DOI: 10.1055/s-0031-1296450
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Editio Cantor Verlag Aulendorf (Germany)

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

A case using bicifadine, a non-narcotic analgesic, as an example
Nuggehally R. Srinivas
1   Integrated Drug Development, Suramus Biopharm, Bangalore, (India)
,
Preeti Ahlawat
2   Clintec International (India) Pvt Ltd, Koramangala, Bangalore, (India)
› Author Affiliations
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Publication History

Publication Date:
13 December 2011 (online)

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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 (CLiv and CLoral) and volume of distribution (Vz). 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 CLiv,Vz, and CLoral were predicted by allometric equations: 1.5252W0.742 (R2 = 0.9989), 1.3489W0.8484 (R2 = 0.9896), 3.2516W0.7694 (R2 = 0.9875), respectively. The absolute bioavailability for bicifadine was estimated to be approximately 67%. The predicted CLoral (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
 

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