Thymidine and thymine in biologic fluids during high-dose infusions of thymidine in mice, monkeys, and man.

Overview

Measurements were made to determine if millimolar thymidine (TdR) concentrations, shown to have antitumor activity in vitro, could be attained in vivo. An adaptation of an ion-exclusion liquid chromatography method was used to quantitate TdR and thymine in various biologic fluids. Millimolar concentrations of TdR were attained in plasma of mice, monkeys, and man by constant infusions of large quantities of TdR (approximately 80 g/m2/day). Cerebrospinal fluid concentrations of TdR at equilibrium were one tenth of the plasma concentration in the monkey. The primary route of removal of TdR at these high plasma concentrations is kidney clearance of intact TdR. Metabolism, which plays a major role in the clearance of TdR at micromolar concentrations in plasma, appears to be saturated at millimolar concentrations of TdR.