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Abstract

Warfarin, an extensively used anticoagulant predates criteria promulgated by regulatory bodies ensuring bioequivalence between products. Coumadin and Marevan, the only two brands prescribed in Australia were tested for dissolution at pH 1.2, 4.5, 6.8, and fed state simulating gastric fluid (FeSSGF; pH 5) using USP Apparatus 2 (paddle type) and an agitation speed of 100 rpm. The dissolution rate for Marevan was faster than for Coumadin after 30 min at each pH tested (pH 6.8; 0.190 vs 0.155, pH 4.5; 0.085 vs 0.017, pH 1.2; 0.109 vs. 0.017 and FeSSGF; 0.254 vs. 0.066 mg/ml/min, respectively). This data was used to model systemic absorption rate and hence, the expected plasma levels of these drugs. Using a one compartment open model with first order absorption for 1,000 patients, results for Gaussian distribution for variable Ka, CL, and Vd, showed no significant difference when comparing AUCtot or Cmax (mean ± SD; 47.57±23.51 vs. 49.16±24.02 mg.h/L and 0.95±0.40 vs. 0.84±0.33 mg/L for Marevan and Coumadin respectively, p=0.06). Interim data (n=20) showed no significant difference between efficacy and safety of Coumadin and Marevan with similar numbers of International Normalized Ratio values falling within target range (65.50% and 58.10% respectively). Adverse event frequency was comparable (14.28% and 11.54% respectively) all been mild. These results confirm the results obtained from the simulated plasma level with no difference between Coumadin and Marevan. However, in clinical practice, more data are needed to conclude whether they can be used to interchangeably emphasising the importance of the collection of clinical trial data.

Biography

Rachada To-a-nan finished her Bachelor and Master degree in Pharmacy from Chiang Mai University, Thailand. She has received the Royal Thai Government scholarship to pursue her PhD at University of South Australia at present. She has been working for Thai Food and Drug Administration in New Drug Department, Bureau of Drug Control.