COMPARATIVE BIOAVAILABILITY STUDY WITH TWO SODIUM VALPROATE TABLET FORMULATIONS IN HEALTHY SUBJECTS
Abstract
The aim was to assess the comparative bioavailability of two formulations (200 mg tablet) of sodium valproate in healthy subjects. This open label randomized, two periods, two treatments, two sequence, 2-way crossover design study was conducted in 18 healthy Indian adult subjects. Subjects received sodium valproate 200 mg of either test or reference formulation with a washout period of 7 days. After study drug administration, serial blood samples were collected over a period of 60 hours. Plasma concentrations of Valproic acid were measured by pre-validated LC-MS-MS method. Pharmacokinetic (PK) parameters Cmax, Tmax, t1/2, AUC0-t, AUC 0-∞, and kel were determined for the 2 sodium valproate formulations. Cmax, AUC0-t, and AUC0-∞ were used to test for bioequivalence after log-transformation of plasma data. The formulations were to be considered bioequivalent if the log-transformed ratios of Cmax, AUC0-t, and AUC0-∞ were within the predetermined bioequivalence range of 80% to 125%. A total of 18 healthy subjects were enrolled. No significant differences were found based on analysis of variance, with mean values and 90% confidence intervals of test/reference ratios for these parameters as follows: Cmax, 15.64 versus 15.20μg/ml (90.79 to 115.45); AUC0-t, 72.71 versus 66.95μg.h/ml (96.03 to 124.87); and AUC0-∞, 105.65 versus 98.11μg.h/ml (94.61 to 124.75). In these healthy Indian subjects, results from the PK analysis suggested that the test and reference formulations of sodium valproate 200 mg tablets were bioequivalent. Both the formulations were well tolerated.
Keywords:
Bioavailability, Bioequivalence, Pharmacokinetics, Sodium Valproate.DOI
https://doi.org/10.25004/IJPSDR.2011.030206References
2. Food and Drug Administration (FDA). Valproate. Major Drug Information Pages. http://www.fda.gov/cder/indexhtml. Accessed January 18, 2009.
3. Akira Fujii, Norio Yasui-Furukori, Taku Nakagami, Takenori Niioka, Manabu Saito, Yasushi Sato and Sunao Kaneko. Comparative in vivo bioequivalence and in vitro dissolution of two valproic acid sustained-release formulations. Drug Des Devel Ther. 2008; 2:139-144.
4. Zaccara G, Messori A, Moroni F. Clinical pharmacokinetics of valproic acid-1988. Clin Pharmacokinet. 1988; 15:367-389.
5. Pollack GM, McHugh WB, Gengo FM. Accumulation and washout kinetics of valproic acid and its active metabolites. J Clin Pharmacol. 1986; 26:668-676.
6. Dhanaraj M, Jayavelu A. Non-equivalence of bioavailability between generic and branded form of sodium valproate. Neurol India. 2004; 52:398.
7. Tyre JH, Eadie MJ, Sutherland JM, Hooper WO. Outbreak of anticonvulsant intoxication in an Australia city. Br Med J. 1970; 4:271-273.
8. Revankar SN, Desai ND, Bhat AD, Bolar HV, Sane SP, Gupta C. Comparison of absorption rate and bioavailability of two brands of carbamazepine. J Assoc Physic Ind. 1999; 47:699-702.
9. Editorial. Biological availability of drugs. Lancet 1972; 1:83.
10. Hassan Y, Alfadly SO, Azmin MN, Peh KK, Tan TF, Noorizan AA, Ismail O. Bioequivalence evaluation of two different formulations of ciprofloxacin tablets in healthy volunteers. Singapore Med J. 2007; 48:819-823.
11. Abdallah RM, Alam SM, Awaad FM. Bioequivalence of two brands of ciprofloxacin 750 mg tablets (Sarf and Ciprobay) in healthy human volunteers. Drug Dev Ind Pharm. 2002; 28:423-429.
12. Westlake WJ. Use of confidence intervals in analysis of comparative bioavailability trials. J Pharm Sci. 1972; 61:1340-1341.
13. Dhaneshwar Shep, Ankit Shah, Asmita Nimkar, Rajen Shah, Vijaya Jaiswal. Comparative bioavailability study with two amiodarone tablet formulations in healthy subjects. Int J Res Pharm Sci. 2010; 1:481-485.
14. Rha JH, Jang IJ, Lee KH, Chong WS, Shin SG, Lee N, Myung HJ. Pharmacokinetic comparison of two valproic acid formulations. J Korean Med Sci. 1993; 8:251-256.
Published
Abstract Display: 765 
PDF Downloads: 848 
