title: Skin metabolism established with the use of MetaSite for selected retinoids employed in topical and systemic treatment of various skin disorders and found in cosmeceuticals.
abstract: OBJECTIVE
  Besides being widely used in cosmetics, retinoids are potent therapeutic agents used topically and systemically as anti-acne agents. The aim of this study was to predict with the use of MetaSite the skin metabolism of selected retinoids employed in treatment of skin disorders and found in cosmeceuticals. The following compounds were studied: retinol, retinaldehyde, retinoic acid, retinyl acetate, retinyl palmitate, acitretin, etretinate, adapalene and bexarotene.
  
  
  METHODS
  MetaSite, Molecular Discovery Ltd. is a computational model that enables prediction of cytochrome P450-dependant metabolism. This software indicates atoms in the molecule structure that are mostly vulnerable to metabolic changes and predicts the metabolite structures.
  
  
  RESULTS
  MetaSite indicated that retinol and retinal metabolites were obtained through hydroxylation of the methyl group located in the position 3 of the aliphatic chain, whereas retinoic acid biotransformation would occur principally in the carbon atom situated in the position 4 in the cyclohexene ring. In acitretin molecule, carbon atom of the methoxy group attached to the benzene ring displayed the highest probability of biotransformation. In etretinate, metabolic reactions would occur principally on the carbon atom of the final ethyl group of the molecule.
  
  
  CONCLUSIONS
  MetaSite metabolism predictions for retinoic acid, acitretin, etretinate, adapalene and bexarotene were in agreement with experimental findings. In case of compounds being converted by catalysts other than cytochrome P450 enzymes, the primary metabolites predicted by MetaSite differ from those reported previously. In conclusion, MetaSite is a useful tool that can aid identification of the major metabolites of compounds being administered topically.
authors: Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Karolina
authors: K
authors: Słoczyńska
authors: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Agnieszka
authors: A
authors: Gunia-Krzyżak
authors: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Dorota
authors: D
authors: Żelaszczyk
authors: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Anna M
authors: AM
authors: Waszkielewicz
authors: Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
authors: Henryk
authors: H
authors: Marona
mesh_terms: D017255:Acitretin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000068816:Adapalene / Q000008:administration & dosage / Q000493:pharmacokinetics; D000287:Administration, Topical; D000077610:Bexarotene; D000068937:Cosmeceuticals / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D008658:Inactivation, Metabolic; D012176:Retinoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D012871:Skin Diseases / Q000188:drug therapy; D012984:Software; D013329:Structure-Activity Relationship; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000493:pharmacokinetics; D014801:Vitamin A / Q000378:metabolism / Q000493:pharmacokinetics
chemical_list: D000068937:Cosmeceuticals; D012176:Retinoids; D013764:Tetrahydronaphthalenes; D014801:Vitamin A; D000068816:Adapalene; D003577:Cytochrome P-450 Enzyme System; D000077610:Bexarotene; D017255:Acitretin