ISSN:
1573-904X
Keywords:
parent drug
;
metabolite
;
bioequivalence
;
absorption rate
;
peak concentration
;
time to peak
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The estimation of bioequivalency using metabolite data was investigated for immediate release formulations with drugs exhibiting linear pharmacokinetics and no first-pass effect. This was accomplished by generating parent drug and metabolite plasma level profiles assuming formation and excretion rate-limited pharmacokinetic models with absorption rate constants obtained from bivariate normal distributions and designated random errors. Simulation results indicated that bioequivalence determination using C maxof parent drug and metabolite was independent of the metabolite models as evaluated by confidence interval approach. However, a clear difference with respect to the outcome of bioequivalence evaluation arises depending upon the utilization of C max values for the parent drug and metabolite. The major reason for this disparity was attributed to the minimal effect of the absorption process for the parent drug on the formation of the metabolite. This phenomenon results in an apparent lower intrasubject variability for C max of the metabolite and, in turn, a tighter confidence interval for C max of the metabolite in comparison with the parent drug. The simulated results have been found to be in agreement with the bioequivalency data for acetohexamide, allopurinol, procainamide, and sulindac. In all cases, the interval of the 90% confidence limit for C max of the metabolite is always smaller than that of the parent drug, regardless of the drug pharmacokinetics and the level of error contained in the data.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1015865920043
Permalink
