Differences in single dose phenytoin kinetics between Greenland Eskimos and Danes.

Abstract

Phenytoin (PHT) disposition was studied in Greenland Eskimos and in Caucasians (Danes) in order to reveal possible ethnic differences in the pharmacokinetics. PHT was administered i.v. as a single, subsaturation does to healthy adult volunteers and determined in plasma by thin-layer chromatography. Based on the time/concentration curves obtained, the half-life, volume of distribution, the area under the curve, and the total body clearance were calculated. The protein binding was measured by ultrafiltration. Three groups were studied: Group 1 were Eskimos living in East Greenland, group 2 were Eskimos living in Denmark, and group 3 were comparable Caucasians, as a reference group. The total body clearance of PHT per kg body weight was almost twice as high in Eskimos, irrespective of place of living or sex, compared with the Danish group. The volume of distribution was larger in the Eskimo group, but the protein binding did not differ. The reason for the differences in clearance and volume of distribution between the two ethnic groups is not clear, but the results emphasize that ethnic differences in pharmacokinetics can be of significance. The total body clearance values for PHT in Caucasians found in the present study agreed with results from other European investigations that used the same dose, but different analytical assays.