Comparative bioequivalence study of two isotretinoin soft gel capsule formulations in healthy male volunteers.
OBJECTIVE
To assess the bioequivalence of 2 oral isotretinoin (20 mg) soft gel capsule formulations. The reference preparation was Roaccutan/Roche while the test preparation was A-Cnotren/Pharmaten, Athens, Greece.


METHODS
The study was an open, randomized, 2-period, 2-sequence, 2-treatment crossover, involving 38 healthy male volunteer subjects. All volunteers completed the study. Isotretinoin plasma concentrations were measured by a fully validated HPLC method. Special care was taken through the collection and analysis of the samples due to instability of isotretinoin to light and temperature. Pharmacokinetic parameters used to assess bioequivalence were AUC(0-last), AUC(0-infinity) for the extent of absorption and Cmax and Tmax for the rate of absorption. Statistical evaluation of Cmax, AUC(0-last), AUC(0-infinity) was done after semi-logarithmic transformation by 2-way analysis of variance (ANOVA). Tmax values were tested using the distribution-free Hodges-Lehman interval.


RESULTS
The parametric 90% confidence intervals for ratio T/R ranged from 95.20-103.20% (point estimate 99.10%) for AUC(0-last), 94.57-102.30% (point estimate 98.36%) for AUC(0-infinity) and 94.81-102.90% (point estimate 98.77%) for Cmax, respectively. Based on the results of Tmax, k(el) and t(1/2), too, there were no statistically significant differences.


CONCLUSIONS
As a result, the 2 isotretinoin preparations in accordance with the European Union bioequivalence requirements, are equivalent with respect to rate and extent of absorption.
Georgarakis
M
M
Laboratory of Pharmaceutics and Drug Control, Department of Pharmacy, Aristotle University of Thessaloniki, Thessaloniki, Greece. mgeorgara@hotmail.com
Zougrou
F
F
Tzavara
S
S
Kontopoulos
G
G
Tsiptsios
I
I
D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005782:Gels; D006207:Half-Life; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D013810:Therapeutic Equivalency
D002214:Capsules; D003879:Dermatologic Agents; D005782:Gels; D015474:Isotretinoin