title: 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 300 mg/m(2) administered intravenously over a time period of 10 min. Sequential blood samples were collected at regular intervals over 24 h 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 300 mg/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) µg h/mL; AUC0-∞ = 30.24 (6.19), 215.43 (27.34), and 417.88 (54.81) µg h/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).
authors.affiliation: Clinical Research Organization for Pharmaceutical Products, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. yani_liu@hotmail.com.
authors.forename: Yani
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Clinical Research Organization for Pharmaceutical Products, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Clinical Research Organization for Pharmaceutical Products, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Zhongfang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Clinical Research Organization for Pharmaceutical Products, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Clinical Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wu
authors.affiliation: Clinical Research Organization for Pharmaceutical Products, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Clinical Research Organization for Pharmaceutical Products, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Shi
authors.affiliation: Department of Geriatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. li_yunqiao@126.com.
authors.forename: Yunqiao
authors.initials: Y
authors.lastname: Li
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D044466:Asian People; D004244:Dizziness / Q000139:chemically induced; D005260:Female; D006261:Headache / Q000139:chemically induced; D064368:Healthy Volunteers; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000009:adverse effects* / Q000097:blood; D008297:Male; D012964:Sodium / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood; D055815:Young Adult
chemical_list: D012964:Sodium; D002955:Leucovorin
keywords: Chinese subjects; Disodium folinate; Pharmacokinetics; Tolerability