Evaluation of the Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Pyrimethamine in Healthy Male Subjects of Japanese and European Ancestry

The pharmacokinetics of pyrimethamine have been evaluated in various populations but have not been reported in subjects of Japanese ancestry following administration as a single‐agent tablet. Furthermore, although pyrimethamine pharmacokinetics after a single dose of the single‐agent tablet studied in Western countries have been reported, these studies are old, and the ancestry of the subjects was not specified. Consequently, this study investigated the pharmacokinetics and safety of a single oral 50‐mg dose of pyrimethamine in healthy male subjects of Japanese and European ancestry. Seven subjects of each ancestry group were administered pyrimethamine, along with calcium folinate. After absorption, pyrimethamine was eliminated, with a mean half‐life of 122.8 hours in Japanese subjects and 99.5 hours in European subjects. The mean Cmax and AUC0‐t were 433.8 ng/mL and 59.63 µg·h/mL in Japanese subjects and 372.7 ng/mL and 42.83 µg·h/mL in European subjects. No safety concerns were reported during the study. Although pyrimethamine exposure was slightly higher in subjects of Japanese than of European ancestry, a considerable overlap in the range of parameter values was observed. Considering the range of pyrimethamine exposure reported previously, difference in exposure observed in this study would not be considered of note.