Toxicologic effects of a high dose of thymidine in mice

Abstract

The pharmacologic effects and plasma concentrations produced by the ip administration of high doses of thymidine were determined in CDF 1 mice. Within 15 min after the injection of thymidine at a dose of 4.075 g/kg (between LD0 and LD50), mean arterial blood pressure and heart rate fell precipitously and remained depressed for over 6 hr. During the experimental period, sedation and anuresis were also consistently observed in thymidine-treated mice. After a dose of 4.7 g/kg, millimolar plasma thymidine concentrations were maintained for 16 to 20 hr; by contrast, at a lower but nonlethal dose (3.8 g/kg), millimolar plasma thymidine concentrations were maintained for only 9 hr. It is suggested that sustained elevation of circulating thymidine in the range 1–10 m m for periods greater than 1 2 day may be associated with toxicity in mice.