I. Mahmood et H. Mahayni, A limited sampling approach in bioequivalence studies: application to longhalf-life drugs and replicate design studies, INT J CL PH, 37(6), 1999, pp. 275-281
Citations number
18
Categorie Soggetti
Pharmacology & Toxicology
Journal title
INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
Objectives: The objectives of this study was to develop a limited sampling
model (LSM) to predict the area under the curve (AUC) and the maximum plasm
a concentration (C-max) for the assessment of bioequivalence studies. Metho
ds: Two drugs (A and B) were selected for this purpose. Drug A was chosen t
o test bioequivalence of two formulations with a long half-life (> 35 hours
), whereas drug B was chosen to test the bioequivalence of two formulations
(half-life = 12 hrs) with a replicate design study. The LSM for both drugs
was developed using 5 blood samples each from 15 healthy subjects. The rel
ationship between plasma concentration (independent variable) at selected t
ime points with the AUC or C-max (dependent variable) was evaluated by mult
iple linear regression analysis, The multiple linear regression which gave
the best correlation coefficient (r) for 5 sampling time vs AUC or C-max wa
s chosen as the LSM. The predicted AUC and C-max from the LSM were then use
d to assess bioequivalence of two different formulations of each drug follo
wing a single oral dose. Results: The model provided good estimates of both
AUC and C-max for both drugs. The 90% confidence intervals an log-transfor
med observed and predicted AUC and C-max were comparable for both drugs. Co
nclusions: The method described here may be used to estimate AUC and C-max
for bioequivalence studies for drugs with long half-lives or for highly var
iable drugs which may require replicate design studies without detailed blo
od sampling.