title: Predicting the dermal absorption of thalidomide and its derivatives.
abstract: Concern has been expressed about the ability of simple algorithms to predict skin permeability and hence skin flux. For a series of thalidomide analogues, a number of software packages have been used to predict octanol water partition coefficients. These, in conjunction with molecular weight, have then been used to calculate skin permeability coefficients. These compare favourably with experimental values. Some of the software packages also predict aqueous solubilities, which can be subsequently used to calculate maximum skin flux. The predicted and measured solubilities have been compared together with the maximum fluxes. The results show that software can be used to predict octanol water partition coefficients and aqueous solubilities (more accurately if the melting point of the compound is known) and hence to obtain very reasonable estimates of skin permeation parameters. These are useful in predicting which analogue has the most appropriate properties for dermal delivery; in the case of the thalidomide analogues, it is the methyl-substituted compound that is best.
authors.affiliation: Medway Sciences, NRI, University of Greenwich, Chatham Maritime, UK. jonathan.hadgraft@btinternet.com
authors.forename: J
authors.initials: J
authors.lastname: Hadgraft
authors.forename: C
authors.initials: C
authors.lastname: Goosen
authors.forename: J
authors.initials: J
authors.lastname: du Plessis
authors.forename: G
authors.initials: G
authors.lastname: Flynn
mesh_terms: D000279:Administration, Cutaneous; D000465:Algorithms; D003879:Dermatologic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008970:Molecular Weight; D000442:Octanols / Q000737:chemistry; D010539:Permeability; D012680:Sensitivity and Specificity; D012869:Skin Absorption; D012984:Software; D012995:Solubility; D013792:Thalidomide / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics*; D014867:Water / Q000737:chemistry
chemical_list: D003879:Dermatologic Agents; D000442:Octanols; D014867:Water; D013792:Thalidomide