title: Effect of physicochemical properties of cyclic terpenes on their ex vivo skin absorption and elimination kinetics.
abstract: BACKGROUND
  The terpenes disturb lipid arrangement in the intercellular region of the stratum corneum (SC) that leads to the increased permeability of the skin. This effect is used in technology of transdermal drug forms and depends on physicochemical properties of terpenes and their amounts penetrated to the stratum corneum; however terpenes do not need penetrate into viable skin tissue and this event is not even desired.
  
  
  OBJECTIVE
  To correlate skin absorption and elimination kinetics of four cyclic terpenes, namely alpha-pinene, beta-pinene, eucalyptol and terpinen-4-ol, applied as neat substance with their physicochemical properties.
  
  
  METHODS
  The terpenes were applied onto the human skin in vitro, and after 1-4 h their content in the separated by a tape-stripping method stratum corneum layers and in the epidermis/dermis was determined using GC. Similarly, the amounts of terpenes in the skin were analysed during 4 h following 1 h absorption.
  
  
  RESULTS
  The fastest and progressive penetration into all skin layers was observed for terpinen-4-ol. All studied terpenes are absorbed in the viable epidermis/dermis, however penetration into this layers is time-dependent process, constantly increasing during 4 h. Like for stratum corneum, the largest cumulation in epidermis/dermis was observed for terpinen-4-ol. The elimination of terpenes from the stratum corneum was fast, especially in deeper layers, and much faster if the initial cumulation was small.
  
  
  CONCLUSIONS
  Investigated cyclic terpenes represent different penetration and elimination characteristics and do not permeate across the skin to the acceptor medium due to large cumulation in the skin tissue. The penetration of terpenes into stratum corneum is greater if their log P-value is close to 3.
authors.affiliation: Medical University of Gdansk, Department of Pharmaceutical Technology, Hallera 107, 80-416 Gdansk, Poland. kcal@wp.pl
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Cal
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kupiec
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Sznitowska
mesh_terms: D000328:Adult; D000081008:Bicyclic Monoterpenes; D001643:Bridged Bicyclo Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D002463:Cell Membrane Permeability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003511:Cyclohexanols / Q000493:pharmacokinetics / Q000494:pharmacology; D020405:Dermis / Q000378:metabolism; D004058:Diffusion; D004817:Epidermis / Q000378:metabolism; D000077591:Eucalyptol; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008875:Middle Aged; D039821:Monoterpenes / Q000493:pharmacokinetics / Q000494:pharmacology; D012869:Skin Absorption; D013729:Terpenes / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D000081008:Bicyclic Monoterpenes; D001643:Bridged Bicyclo Compounds; D003511:Cyclohexanols; D039821:Monoterpenes; D013729:Terpenes; C010789:beta-pinene; C034019:terpinenol-4; C005451:alpha-pinene; D000077591:Eucalyptol