title: 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.
  
  
  CONCLUSIONS
  Only the FDA-stipulated standard high-fat, high-calorie meal of 50-g fat was studied in the fed state.
  
  
  CONCLUSIONS
  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.
authors: Department of Dermatology, Jefferson Medical College, Philadelphia, Pennsylvania. Electronic address: guywebster@yahoo.com.
authors: Guy F
authors: GF
authors: Webster
authors: Dermatology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.
authors: James J
authors: JJ
authors: Leyden
authors: Cipher Pharmaceuticals Inc, Mississauga, Ontario, Canada.
authors: Jason A
authors: JA
authors: Gross
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D003879:Dermatologic Agents / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D015474:Isotretinoin / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D004364:Pharmaceutical Preparations; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D003879:Dermatologic Agents; D004364:Pharmaceutical Preparations; D015474:Isotretinoin
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