title: Bioequivalence Study of Warfarin in Healthy Chinese Volunteers With a Validated High-Performance Liquid Chromatography-Mass Spectrometry Method.
abstract: This study was designed to investigate the pharmacokinetics of an innovative film-coated warfarin sodium tablet and to compare it with the marketed sugar-coated warfarin sodium tablet in humans. A single-dose, open-label, randomized, two-way crossover study was performed in 24 healthy Chinese male volunteers. They were administered 2.5 mg of innovative film-coated warfarin sodium tablets or the marketed sugar-coated warfarin sodium tablets. Blood samples were collected at different time points after dosing for investigation of the pharmacokinetics of warfarin in human plasma. A sensitive liquid chromatography mass spectrometry method was established to determine warfarin in plasma. Drug and Statistics 2.1.1 was applied to calculate the pharmacokinetics parameters. The main pharmacokinetic parameters for film-coated and sugar-coated warfarin were the following: t½, 103.5 ± 18.8 and 105.8 ± 21.3 hours; Tmax, 0.7 ± 0.5 and 1.3 ± 0.8 hours; Cmax, 347.8 ± 74.8 and 322.9 ± 75.7 ng/mL; AUC0∼360, 16,024.2 ± 3713.9 and 15,586.6 ± 3477.0 ng·mL-1·h; AUC0∼∞, 17,335.7 ± 4089.1 and 16,912.0 ± 3911.2 ng·mL-1·h, respectively. The human pharmacokinetics of film-coated and sugar-coated warfarin were slightly different. The oral absorption and bioavailability of innovative film-coated warfarin were slightly higher than those of the sugar-coated warfarin. This study is vital to clinical usage of warfarin not only because of the pharmacokinetic parameters of the 2 pharmaceutical dosage forms of warfarin but also to obtain data on the prevalence of CYP2C9 and VKORC1 genes and their influence on the concentration of warfarin.
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China, 250012.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China, 250012.
authors.forename: Fanlong
authors.initials: F
authors.lastname: Bu
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China, 250012.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China, 250012.
authors.forename: Benjie
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China, 250012.
authors.forename: Abdul Sami
authors.initials: AS
authors.lastname: Shaikh
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China, 250012.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China, 250012.
authors.forename: Ruichen
authors.initials: R
authors.lastname: Guo
authors.affiliation: Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong Province, China, 250012.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000097:blood* / Q000494:pharmacology; D044466:Asian People / Q000235:genetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D018592:Cross-Over Studies; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000592:standards*; D013810:Therapeutic Equivalency; D014859:Warfarin / Q000097:blood* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D014859:Warfarin
keywords: HPLC-MS; bioequivalence; gene polymorphism; pharmacokinetics; warfarin