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

作者：Webster Guy F^*; Leyden James J; Gross Jason A

来源：Journal of the American Academy of Dermatology, 2013, 69(5): 762-767.

DOI：10.1016/j.jaad.2013.05.036

• acne
• area under the curve
• bioavailability
• fasting
• fed
• isotretinoin
• maximum measured plasma concentration over sampling time period
• systemic exposure
• time of maximum measured plasma concentration

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). %26lt;br%26gt;Objective: We sought to compare the pharmacokinetic profiles of a new formulation of isotretinoin (isotretinoin-Lidose) with the innovator isotretinoin formulation. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;Limitations: Only the FDA-stipulated standard high-fat, high-calorie meal of 50-g fat was studied in the fed state. %26lt;br%26gt;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.

• 出版日期2013-11