PHARMACOKINETICS AND BIOEQUIVALENCE STUDIES OF WARFARIN SODIUM 5 MILLIGRAMS TABLET IN HEALTY THAI SUBJECTS

Authors

  • Chuleegone Sornsuvit Chiang Mai University
  • Narawadee Niamhun Chiang Mai University
  • Nutthida Luengpiansamut Chiang Mai University
  • Siriluk Sangsrijan Chiang Mai University
  • Wirat Niwatananum Chiang Mai University
  • Sayam Kaewvichit Chiang Mai University
  • Darunee Hongwiset Chiang Mai University
  • Nontakan Nuntachit Chiang Mai University
  • Songwut Yotsawimonwat Chiang Mai University

Keywords:

Pharmacokinetic, Bioequivalence, Warfarin, HPLC, Validation, Human plasma

Abstract

Objective:  The present study aimed to evaluate the bioequivalence between the generic warfarin sodium tablet and a reference product when gave as equal labeled doses in healthy Thai subjects under fasting condition.

Methods:  A randomized, open-label, single dose, two treatments, two periods, two sequences, crossover design between 5 mg of warfarin administration under fasting condition was conducted in 22 male and female healthy Thai subjects. Each subject was assigned randomly to receive a single oral dose of the test formulation or the reference formulation of 5 mg warfarin tablets. Study periods were separated by a 14-day washout period. Blood samples were collected at 0.0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 2.5, 3.0, 4.0, 8.0, 12.0, 24.0, 36.0, 48.0 and 72.0 h after drug administration. A simple, sensitive and specific HPLC method was used for quantification of warfarin in plasma. Pharmacokinetic parameters were analyzed including Cmax, Tmax, t1/2 and AUC0-72h.

Results:  Twenty subjects, selected randomly from healthy adult Thai subjects were enrolled, age of 22.5 + 3.1 years, weight, 59 + 6 kg. Twenty-one subjects completed both periods of the study. The mean Cmax values were 759.63 and 778.20 ng/ml and the mean AUC0-72h were 20010.89 and 20418.55 ng. h./ml for test and reference formulations, respectively. The mean ratios for log-transformed data were 0.9955 and 0.9971 for Cmax, and AUC0-72h, respectively. The 90% confidence intervals of the ratios of Cmax and AUC0-72h between test and reference tablets were 88.23% – 105.70% and 94.40% – 99.61%.

Conclusion:  It can be concluded that test and reference warfarin 5 mg products were bioequivalent in terms of rate and extent of absorption.

 

Downloads

Download data is not yet available.

References

McEvoy GK, Show ED, editors. AHFS drug information. Bethesda, MD: American society of health-system pharmacists; 2011. p. 1461-77.

Mhra public assessment report warfarin: changes to product safety information Dececmber 2009; Available from: URL: http://www.mhra.gov. uk/home/groups/plp/documents/websiteresources/con065506.pdf) [Assessed on April. 23, 2012]

Yacobi A, Masson E, Moros D, Ganes D, Lapointe C, Abolfathi Z, et al. Who needs individual bioequivalence studies for narrow therapeutic index drugs? A case for warfarin. J Clin Pharmcol 2000;40:826-35.

Takahashi H, Kashima T, Kimura S, Muramoto N, Nakahata H, Kubo S, et al. Determination of unbound warfarin enantiomers in human plasma and 7-hydroxywarfarin in human urine by chiral stationary-phase liquid chromatography with ultraviolet or fluorescence and on-line circular dichoism detection. J Chromatogr B 1997;701:71-80.

Ring PR, Bostick JM. Validation of a method for the determination of (R)-warfarin and (S)-warfarin in human plasma using LC with UV detection. J Pharm Biomed Anal 2000;22:573-81.

Boppana VK, Schaefer WH, Cyronak MJ. High-performance liquid-chromatographic determination of warfarin enantiomers in plasma with automated on-line sample enrichment. J Biochem Biophys Methods 2002;54:315-26.

Lombardi R, Chantarangkul V, Cattaneo M, Tripodi A. Measurement of warfarin in plasma by high performance liquid chromatography (HPLC) and its correlation with the international normalized ratio. Thromb Res 2003;111:281-4.

Radwan MA, Bawazeer GA, Aloudah NM, AI Quadeib BT, Aboul-Enein HY. Determination of free and total warfarin concentrations in plasma using UPLC MS/MS and its application to a patient samples. Biomed Chromatogr 2012;26:6-11.

Guideline on the investigation of bioequivalence. European medicine agency. London; 2010.

US Food and drug administration. Guidance for industry: Bioavailability and bioequivalence studies for orally administered drug products-general consideration; 2003.

Akamine Y, Uno T. Warfarin enantiomers pharmacokinetics by CYP2C19. In: Gallelli L, editor. Pharmacology. [Internet] Croatia: In Tech; 2012 [cited 2014 December]. 720p. Available from: http://www.intechopen.com/books /pharmacology/ the-effect-of-cyp2c19-genotypes-on-the-pharmacokinetics-of-warfarin-enantiomers.

Maddison J, Somogyi AA, Jensen BP, James HM, Gentgall M, Rolan PE. The pharmacokinetics and pharmacodynamics of single dose (R)-and (S)-warfarin administered separately and together: relationship to VKORC1 genotype. Br J Clin Pharmacol 2012;75(1):208-16.

Jaruchotikamol A. Warfarin and genetic polymorphism. Thai Pharm Health Sci J 2010;5(2):180-4.

Drug control division, Food and drug administration, Ministry of Public Health, Thailand. Guideline for the conduct of bioavailability and bioequivalence studies; 2009.

Published

01-03-2015

How to Cite

Sornsuvit, C., N. Niamhun, N. Luengpiansamut, S. Sangsrijan, W. Niwatananum, S. Kaewvichit, D. Hongwiset, N. Nuntachit, and S. Yotsawimonwat. “PHARMACOKINETICS AND BIOEQUIVALENCE STUDIES OF WARFARIN SODIUM 5 MILLIGRAMS TABLET IN HEALTY THAI SUBJECTS”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 7, no. 3, Mar. 2015, pp. 219-22, https://innovareacademics.in/journals/index.php/ijpps/article/view/4532.

Issue

Section

Original Article(s)