Percutaneous absorption in man: in vitro-in vivo correlation. 2011

P A Lehman, and S G Raney, and T J Franz
Pre-Clinical Dermatology, Cetero Research, Fargo, N. Dak., USA.

OBJECTIVE To examine the existing literature to determine the degree to which percutaneous absorption data obtained using the excised human skin model match those obtained from living man. METHODS The scientific literature was reviewed to collect data on compounds whose percutaneous absorption through human skin had been measured under both in vitro and in vivo conditions. The in vitro-in vivo (IVIV) correlation was evaluated by computing the in vitro/in vivo ratio using total absorption (percent of applied dose) as the metric for comparison. RESULTS A total of 92 data sets were collected from 30 published studies. The average IVIV ratio across all values was 1.6, though for any single data set there could be a nearly 20-fold difference between the in vitro and in vivo values. In 85% of the cases, however, the difference was less than 3-fold. The correlation was significantly improved when data were excluded from studies in which the protocols for both studies were not fully harmonized. For harmonized data sets the average IVIV ratio was 0.96 and there was a less than 2-fold difference between the in vitro and in vivo results for any one compound, with IVIV ratios ranging from 0.58 to 1.28. The dominant factors leading to exclusion of data were the use of skin from different anatomical sites and vehicles of differing composition. CONCLUSIONS Percutaneous absorption data obtained from the excised human skin model closely approximate those obtained from living man when the two study protocols are appropriately matched.

UI MeSH Term Description Entries
D008297 Male Males
D010599 Pharmacokinetics Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology. ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012867 Skin The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
D012869 Skin Absorption Uptake of substances through the SKIN. Absorption, Skin,Intracutaneous Absorption,Intradermal Absorption,Percutaneous Absorption,Transcutaneous Absorption,Transdermal Absorption,Absorption, Intracutaneous,Absorption, Intradermal,Absorption, Percutaneous,Absorption, Transcutaneous,Absorption, Transdermal,Absorptions, Intracutaneous,Absorptions, Intradermal,Absorptions, Percutaneous,Absorptions, Skin,Absorptions, Transcutaneous,Absorptions, Transdermal,Intracutaneous Absorptions,Intradermal Absorptions,Percutaneous Absorptions,Skin Absorptions,Transcutaneous Absorptions,Transdermal Absorptions
D013223 Statistics as Topic Works about the science and art of collecting, summarizing, and analyzing data that are subject to random variation. Area Analysis,Estimation Technics,Estimation Techniques,Indirect Estimation Technics,Indirect Estimation Techniques,Multiple Classification Analysis,Service Statistics,Statistical Study,Statistics, Service,Tables and Charts as Topic,Analyses, Area,Analyses, Multiple Classification,Area Analyses,Classification Analyses, Multiple,Classification Analysis, Multiple,Estimation Technic, Indirect,Estimation Technics, Indirect,Estimation Technique,Estimation Technique, Indirect,Estimation Techniques, Indirect,Indirect Estimation Technic,Indirect Estimation Technique,Multiple Classification Analyses,Statistical Studies,Studies, Statistical,Study, Statistical,Technic, Indirect Estimation,Technics, Estimation,Technics, Indirect Estimation,Technique, Estimation,Technique, Indirect Estimation,Techniques, Estimation,Techniques, Indirect Estimation
D014677 Pharmaceutical Vehicles A carrier or inert medium used as a solvent (or diluent) in which the medicinally active agent is formulated and or administered. (Dictionary of Pharmacy, 1986) Pharmaceutical Vehicle,Vehicle, Pharmaceutical,Vehicles, Pharmaceutical

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