ISSN:
1573-904X
Keywords:
bioequivalence
;
absorption rate
;
extended-release
;
mean absorption time
;
relative dispersion
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Purpose. The sensitivity and effectiveness of indirect metrics proposedfor the assessment of comparative absorption rates in bioequivalencestudies [C max , T max , partial AUC(AUC p ), feathered slope (SL f ), interceptmetric (I)] were originally tested by assuming first-order absorption.The present study re-evaluates their sensitivity performances using themore realistic inverse Gaussian (IG) model characterizing the inputprocess for oral drug administration. Methods. Simulations were performed for both the first-order orexponential model (EX) which is determined by only one parameter, themean absorption time (MAT = 1/k a ), and the IG model, whichadditionally contains a shape parameter, the relative dispersion of absorptiontime distribution (CV 2 A ). Kinetic sensitivities (KS) of the indirectmetrics were evaluated from bioequivalence trials (error free data)generated with various ratios of the true parameters (MAT and CV 2 A ) of thetwo formulations. Results. The behavior of the metrics was similar with respect tochanges in MAT ratios with both models: KS was low with C max ,moderate with SL f and AUC p , and high with I and T max followingcorrection for apparent lag time (T lag ). Changes of the shape parameterCV 2 A , however, were not detectable by C max , T max , SL f , and AUC p .Changes in both MAT and CV 2 A were well reflected by I with CV 2 A - ratio〉 1. I exhibited approximately full KS also with CV 2 A - ratio 〈1 when a correction was first applied for the apparent lag time. Conclusions. The time profile of absorption rates is insufficientlycharacterized by only one parameter (MAT). Indirect metrics which aresensitive enough to detect changes in the scale and shape of the inputprofile could be useful for bioequivalence testing. Among the testedmeasures, I is particularly promising when a correction is appliedfor T lag .
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1007521016985
Permalink
