Methodology On Bioequivalence Study Of Shorter Wash-out Period For Drugs With Long Elimination Half-life

Bioequivalence study is an important way of evaluating quality of drug, which isapplied to new drug application and plays a significant role in the process of new drugdevelopment and preparation formulation alteration. Pharmacokinetic measure is afrequently used way of assessing bioequivalence, in which area under theconcentration-time curve is a key parameter. In a typical bioequivalence study, atwo-period, two-sequence single dose crossover design is the design of choice. In acrossover design, the treatment periods should be separated by an adequate wash-outperiod to avoid residual effect of drug. Drug with long elimination half-life is ourobject of study, for which an extremely long wash-out period is required according totraditional regulations. Long study period may bring about some adverse factors.Aiming at the problem, this study developed new methods of calculating theparameter on condition of a shorter wash-out period. Crossover design was appliedwith a shorter wash-out period in our study. We tested our method using computersimulation and made validations using clinical data. Wash-out period is shortened to1.5times and1time of half-life from7times long of half-life in this study. The resultshowed that the parameter can be accurately calculated with our new method whenthe wash-out period is shortened to1.5times long of half-life.The new method could shorten the trial period and cut the cost, meanwhile, itcould ensure the accuracy and stability of evaluation parameter. We consider it as afeasible method to evaluate bioequivalence of two drugs. Whether the new methodcan replace the current one in the evaluation of bioequivalence needs vast testsespecially clinical tests.