title: Simple rules defining the potential of compounds for transdermal delivery or toxicity.
abstract: OBJECTIVE
  Simple rules based on readily accessible physicochemical properties enable identification of solutes that penetrate skin very slowly or rapidly.
  
  
  METHODS
  Literature in vitro maximal flux values (Jmax) across human skin were collected for 87 penetrants. Penetrants were assigned as "good" (Jmax > 10(-5.52) mole x cm(-2) x h(-1)), "bad" (Jmax < 10(-8.84) mole x cm(-2) x h(-1)) or "intermediate" based on mean +/- 1SD. The feasibility of using readily available physicochemical properties, such as molecular weight (MW), melting point (MP, degrees K), octanol-water partition coefficient (K), water solubility (S, molarity), number of atoms available for H-bonding (HB), in assigning solutes was examined.
  
  
  RESULTS
  Good penetrants had MW < or = 152, log S > -2.3, HB < or = 5, log K < 2.6, MP < or = 432. Bad penetrants had MW > 213, log S < -1.6, HB > or = 4, log K > 1.2, MP > or = 223. Discriminant analysis using MW, HB, log K correctly assigned 70% of compounds. Individual success rates were good (88%), intermediate (58%), bad (93%). Aqueous Jmax data for 148 test solutes were used for validation. Discriminant analysis assigned 76% of compounds, with individual rates of good (76%), intermediate (67%), and bad (97%). No good penetrants were misclassified as bad or vice versa.
  
  
  CONCLUSIONS
  These rules enable rapid screening of potential drug delivery candidates and environmental exposure risks.
authors.affiliation: Therapeutics Research Unit, Southern Clinical Division, University of Queensland, Princess Alexandra Hospital, Brisbane, QLD 4102, Australia.
authors.forename: Beatrice M
authors.initials: BM
authors.lastname: Magnusson
authors.forename: W John
authors.initials: WJ
authors.lastname: Pugh
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
mesh_terms: D000279:Administration, Cutaneous; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D006860:Hydrogen Bonding / Q000187:drug effects; D008422:Materials Testing / Q000379:methods* / Q000592:standards*; D008970:Molecular Weight; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods; D044366:Transition Temperature / Q000187:drug effects
chemical_list: D014677:Pharmaceutical Vehicles