Tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects: an open-label, randomized, single-center study.

Abstract

The tolerability and pharmacokinetics of disodium folinate may vary with different races, and these variations might result in different outcomes. This study assessed the tolerability and pharmacokinetics of disodium folinate following single intravenous doses in healthy Chinese subjects, with gender factor also taken into account. Subjects were randomized to receive a single dose of disodium folinate at 20, 200, or 300mg/m(2) administered intravenously over a time period of 10min. Sequential blood samples were collected at regular intervals over 24h after dosing and were analyzed using a validated high-performance liquid chromatography (HPLC) method. Pharmacokinetic parameters, including C max, AUC0-t, t 1/2, V d, and CL, were calculated using non-compartmental models. Tolerability was assessed by collecting adverse events (AEs) and monitoring vital signs, physical examinations, laboratory tests, and electrocardiograms. Following a single intravenous administration of disodium folinate 20, 200, and 300mg/m(2), the mean (standard deviation) pharmacokinetic parameters were as follows: C max=5.18 (0.58), 47.80 (10.10), and 69.93 (9.72)µg/mL; AUC0-t=25.85 (3.36), 194.53 (30.18), and 355.26 (35.31) µgh/mL; AUC0-∞=30.24 (6.19), 215.43 (27.34), and 417.88 (54.81) µgh/mL; t 1/2=8.77 (2.57), 7.64 (1.81), and 9.08 (1.64)h; CL=1.12 (0.18), 1.55(0.25), and 0.78 (0.09) L/h; V d=13.75 (2.61), 17.38 (6.44), and 10.05 (1.49) L, respectively. The mean C max, AUC0-t, and AUC0-∞ increased in a dose-proportional manner. No significant differences in pharmacokinetic parameters were noted by gender. The most common AEs reported were mild redness at the injection site and neurological symptoms (headache, dizziness, and fatigue).