INTERSPECIES SCALING - PREDICTING PHARMACOKINETIC PARAMETERS OF ANTIEPILEPTIC DRUGS IN HUMANS FROM ANIMALS WITH SPECIAL EMPHASIS ON CLEARANCE

The objective of this study was to test the interspecies-scaling appro ach in a series of antiepileptic drugs. Clearance, volume of distribut ion, and elimination half-life were scaled up from animal data obtaine d from literature. Four different methods were utilized to generate pl ots to scale up the clearance values: (i) clearance vs body weight (si mple allometric equation); (ii) the product of clearance and maximum l ife-span potential (MLP) vs body weight (an approach recommended in li terature); (iii) the two-term power equation which incorporates both b ody weight and brain weight suggested by Boxenbaum; and (iv) the produ ct of clearance and brain weight vs body weight (a new approach being introduced in this study). When the predicted values for clearance wer e qualitatively compared with the observed values in humans, it was fo und that our proposed method predicted the clearance better than the o ther three methods. Using the simple allometric equation, the predicti on of volume of distribution as a function of body weight was found to be satisfactory. The elimination half-life could not be predicted fro m simple allometric equations for any of the drugs studied; however, u tilizing the equation CL = VK, prediction for half-life was feasible. The results of this study indicate that it is possible to predict reli ably the pharmacokinetic parameters of these antiepileptic drugs in hu mans from animal data using an allometric approach.