Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, 4-treatment, crossover study

Abstract

Background: A high-fat meal is needed for optimal absorption of isotretinoin. A new formulation of isotretinoin, which enhances absorption of isotretinoin in the absence of dietary fat, has recently been approved by the Food and Drug Administration (FDA).

Objective: We sought to compare the pharmacokinetic profiles of a new formulation of isotretinoin (isotretinoin-Lidose) with the innovator isotretinoin formulation.

Methods: This study was an open-label, single-dose, randomized, 4-treatment, crossover comparative trial between a new and innovator formulation of isotretinoin in the fasting and fed states.

Results: Both formulations were bioequivalent under fed conditions. As expected in a fasting state, absorption of both formulations was reduced. A considerable difference between the 2 drugs occurred under fasted conditions-there was a marked improvement in overall bioavailability of the isotretinoin-Lidose formulation. Mean plasma levels of the isotretinoin-Lidose formulation during fasting reached 66.8% of that observed with a fatty meal, and those of the isotretinoin formulation only reached 39.6% of that observed with a fatty meal.

Limitations: Only the FDA-stipulated standard high-fat, high-calorie meal of 50-g fat was studied in the fed state.

Conclusion: Isotretinoin-Lidose formulation is bioequivalent to the innovator formulation under fed conditions with regard to its pharmacokinetic profile but delivers twice as much isotretinoin and 4-oxo-isotretinoin when administered after an overnight fast.

Keywords: AUCi; AUCt; BA; BE; Cmax; FDA; Food and Drug Administration; Tmax; acne; area under plasma concentration versus time curve from time zero (0 hour) to time of last measurable plasma concentration, calculated by linear trapezoidal method; area under plasma concentration verus time curve from time zero (0 hour) to infinity (AUCi calculated as sum of AUCt + measured plasma concentration at time of last measurable plasma concentration/apparent first order elimination rate constant); area under the curve; bioavailability; bioequivalent; fasting; fed; isotretinoin; maximum measured plasma concentration over sampling time period; systemic exposure; time of maximum measured plasma concentration.