Effects of different dose schedules of amethopterin on serum and tissue concentrations and urinary excretion patterns

Abstract

The highest serum concentration of amethopterin after single intravenous administration was present in the first specimen, which was obtained at 30 minutes. Total urinary output was greater the first 8 hours than during the next 16 hours. Tissue specimens of skin contained greater amounts of amethopterin at 5 hours than at 10 to 12 hours. In contrast to single intravenous injection, 12 hour intravenous or intra‐arterial infusion of the same dose produced serum concentrations of the drug which were sustained until the infusion was completed. The total urinary output of the drug was less in the first 8 hours than in the remaining 16 hours. As the infusion progressed, specimens of skin tissue showed increased concentrations of the drug. The results of this study suggest that the enhanced biologic activity of amethopterin noted clinically on continuous administration is related to sustained serum and tissue concentrations of the drug.