Guy F Webster1, James J Leyden2, Jason A Gross3. 1. Department of Dermatology, Jefferson Medical College, Philadelphia, Pennsylvania. Electronic address: guywebster@yahoo.com. 2. Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. 3. Cipher Pharmaceuticals Inc, Mississauga, Ontario, Canada.
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.
RCT Entities:
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
Authors: Caroline S Costa; Ediléia Bagatin; Ana Luiza C Martimbianco; Edina Mk da Silva; Marília M Lúcio; Parker Magin; Rachel Riera Journal: Cochrane Database Syst Rev Date: 2018-11-24