Interspecies Scaling of the Pharmacokinetic Parameters of Cocaine and Application to Pharmacokinetics in Man

The literature was reviewed for pharmacokinetic studies of cocaine in any species from 1966 to 1994. Fourteen studies were identified as either presenting pharmacokinetic parameters or having sufficient data to calculate the pharmacokinetic parameters using model-independent techniques. Clearance and volume of distribution were successfully scaled using a power function of total body weight, whereas half-life was independent of total body weight. The allometric model suggested that sheep may be dissimilar to other species in terms of cocaine disposition. The allometric estimates were applied to a recently developed physiological-based pharmacokinetic model for cocaine pharmacokinetics and found to be predictive of cocaine pharmacokinetics in man. These findings provide further evidence that the pharmacokinetics of drugs follow well-defined, size-related physiological relationships, and that the use of allometric scaling in preclinical drug development may provide reasonable estimates of drug disposition in man.