Bioequivalence study of a film-coated tablet of deferiprone in healthy Thai volunteers

Abstract

Objective: To evaluate the bioequivalence of a single dose of deferiprone tablet manufactured locally (GPO-L-ONE®, GPO, Thailand) with a reference formulation (Ferriprox®, ApoPharma, Canada). Volunteers and methods: A randomized, single dose, two-treatment, two-period, two- sequence crossover study was conducted in 24 healthy volunteers. Each subject received a single dose of 3 tablets of 500 mg deferiprone of both formulations with a two-week washout period. Blood samples were collected at 12 points for 480 min. Serum deferiprone levels were analyzed using high performance liquid chromatography (HPLC) method. Pharmacokinetic parameters were calculated from serum concentration-time curve and applying the non-compartment model. Statistical comparisons of Cmax, AUC0-t, AUC0-infvalues were evaluated after logarithmic transformation. Other pharmacokinetic parameters were tested non-parametrically. Results: The Cmaxvalue (mean ± SD) for reference and test product was 32.4 ± 13.2 and 27.8 ± 12.8 μg/ml, respectively. Mean ratio (test/reference) of Cmaxwas 0.852 with 90% CI of 0.772 - 0.934. Mean ratio (test/reference) of AUC0-twas 0.962 with 90% CI of 0.914 to 1.012, and of AUC0-infwas 0.966 with 90% CI of 0.918-1.016. Both formulations were well tolerated and no adverse effects were observed. Conclusion: The 90% CI of mean ratio of AUC0-tand AUC0-inffell within the acceptable range (0.80 - 1.25) for bioequivalent eligibility. Regarding the efficacy of deferiprone, which depends on AUC rather than Cmax, 90% CI of mean ratio of Cmaxwas within the acceptable range of WHO criteria for bioequivalence study (0.75 - 1.33). Therefore the two film-coated formulations of deferiprone tablet were proven bioequivalent in healthy Thai volunteers. © 2009 Dustri-Verlag Dr. K. Feistle.