BACKGROUND
Isotretinoin, the first line therapy for the treatment of severe nodular acne, is recommended to be administered with meals to optimize its bioavailability and efficacy. To overcome this limitation, low-dose micronized-isotretinoin is formulated by using an optimized micronization technology that enhances the rate of dissolution and bioavailability of isotretinoin.
OBJECTIVE
To assess the comparative bioavailability of low-dose micronized-isotretinoin 16mg (Test;T) and conventional isotretinoin 20mg (Reference;R) under fasting condition.
METHODS
An open label, randomized, two-treatment, two-period, two-sequence, single-dose, cross-over comparative bioavailability study. Study period involved fasting for at least 10hours prior to administration and 4hours after a single oral dose of either test or reference product. The interval between dosing (washout period) was 18days.
RESULTS
Total 15 participants completed the study. The Cmax was 439.58±169.99ng/mL and 149.64±26.91ng/mL; and AUC0–∞ was 6181.90 ± 2240.75ng·h/mL and 2479.83 ± 975.90ng·h/mL for test and reference, respectively. The ratio of T/R [90 %CI] were 277.78% (238.11-324.06) for Cmax, and 246.95% (228.93-266.39) for AUC0–∞. The Median Tmax was 3.25hrs and 2.75hrs test and reference formulation respectively. Both the formulations were well tolerated.
CONCLUSIONS
Low-dose micronized-isotretinoin 16mg had ~2.5 folds higher bioavailability as compared to conventional isotretinoin 20mg under fasting conditions.