Pharmacokinetics of rac‐leucovorin vs [S]‐leucovorin in patients with advanced gastrointestinal cancer.

1. The pharmacokinetics of [R]‐leucovorin ([R]‐LV), [S]‐leucovorin ([S]‐ LV) and the circulating metabolite [S]‐5‐methyltetrahydrofolate ([S]‐5‐ MTHF) were studied after administration of racemic LV and [S]‐LV in 21 subjects. 2. After intravenous infusion of 600 mg m‐2 rac‐LV (group 1, n = 7) or 300 mg m‐2 [S]‐LV (group 3, n = 7), the decay of [S]‐LV in plasma was biexponential with a distribution half‐life of 0.8 to 1 h and an elimination half‐life of 11 to 23 h. When rac‐LV was administered as a 2 h i.v. infusion (400 mg m‐2) following a loading dose of 200 mg m‐2 (group 2, n = 7), the plasma concentrations of [R]‐ LV and [S]‐5‐MTHF decayed monoexponentially with mean (+/‐ s.d.) half‐ lives of 10 +/‐ 3 h and 7 +/‐ 2 h, respectively. 3. The AUC of [S]‐5‐ MTHF was significantly higher after infusion of 300 mg m‐2 [S]‐LV than after infusion of 600 mg m‐2 rac‐LV (83 +/‐ 22 micrograms ml‐1 h vs 53 +/‐ 22 micrograms ml‐1 h; P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)