Subscribe to RSS
DOI: 10.1055/s-0031-1298024
Comparative Bioequivalence Study of Leflunomide Tablets in Indian Healthy Volunteers
Publication History
received 14 October 2011
accepted 07 December 2011
Publication Date:
25 January 2012 (online)
Abstract
Objective:
The pharmacokinetics of teriflunomide [CAS No. 163451-81-8], the metabolite of leflunomide [CAS No. 75706-12-6] has been evaluated in adult human volunteers after oral administration of tablet formulation. However, no published data is available regarding the bioavailability of this in the Indian population. In light of the above, a study was designed to carry out a bioequivalence study of 2 preparations of leflunomide 20 mg in healthy Indian male volunteers.
Methods:
24 healthy male volunteers (age, 25±4.1 years; weight, 57.58±7.01 kg) were enrolled in this study. Each subject received a test and reference formulation in a single dose, fasting 2 period, 2 way crossover study with a wash out period of 4 weeks. Analysis of teriflunomide from plasma samples was done by a simple and sensitive HPLC method using UV detection developed in our laboratory. An analysis of variance was performed on the pharmacokinetic parameters Cmax, AUC0-t, AUC0–∞ using GLM procedures in which sources of variation were subject, formulation, and period.
Results:
The results indicated that there are no statistically significant differences between the 2 products in either the mean concentration-time profiles or in the obtained pharmacokinetic parameters. 90% confidence limits for the log transformed data of Cmax, AUC0–t, AUC0–∞. were within the acceptable range of 0.80–1.25.
Conclusion:
The results indicate that the 2 products are bioequivalent in terms of rate and extent of drug absorption. Both the preparations were well tolerated with no adverse reactions throughout the study.
-
References
- 1 Goldenberg MM. Clin Ther 1999; 21: 1837
- 2 Olsen NJ, Strand V, Kremer JM. Bull Rheum Dis 1999; 48: 1
- 3 Kaplan MJ. Curr Opin Investig Drugs 2001; 2: 222
- 4 Fox RI. J Rheumatol Suppl 1998; 25 (Suppl. 53) 20
- 5 Rozman B. Clinical pharmacokinetics of leflunomide, Clin. Pharmacokinet 2002; 41: 421-430
- 6 van Roon EN, Jansen TL, van de Laar MA et al. Therapeutic drug monitoring of A77 1726, the active metabolite of leflunomide: serum concentrations predict response to treatment in patients with rheumatoid arthritis. Ann Rheum Dis. 2005 64. 569-574
- 7 Schmidt A, Schwind B, Gillich M et al. Simultaneous determination of leflunomide and its active metabolite, A77 1726, in human plasma by high-performance liquid chromatography. Biomed Chromatogr. 2003 17. 276-281
- 8 Chow SC, Liu JP. Design & Analysis of Bioavailability & Bioequivalence Studies. Marcel Dekker; New York: 2000: 1-6
- 9 Abdon HM. Dissolution, Bioavailability & Bioequivalence, Mack Printing. Easton 1989; 481-490
- 10 Hauschke D, Steinijans VW, Diletti E. A distribution free procedure for the statistical analysis of bioequivalence studies. International Journal of Clinical Pharmacology, Therapy and Toxicology 1990; 28 (02) 72-78
- 11 Schulz HU, Steinijans VW. Striving for standards in bioequivalence assessment: a review. International Journal of Clinical Pharmacology, Therapy and Toxicology 1992; 30 (01) S1-S6
- 12 Nation RL, Sansom LN. Bioequivalence requirements for generic products. Pharmacol Ther 1994; 62: 41-55
- 13 Shah VP, Midha KK, Sighe S. Analytical method validation: bioavailability, bioequivalence and pharmacokinetic studies. Eur J Drug Metab Pharmacokin 1992; 16: 249-255