Percutaneous Absorption in Man: In vitro-in vivo Correlation

Aims: 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.

[1]  J. Cocker,et al.  The in vitro percutaneous penetration of chiorpyrifos , 2000, Human & experimental toxicology.

[2]  S. Hotchkiss,et al.  Comparativein VitroSkin Absorption and Metabolism of Coumarin (1,2-Benzopyrone) in Human, Rat, and Mouse , 1997 .

[3]  H. Maibach,et al.  Regional variation in percutaneous penetration of 14C cortisol in man. , 1967, The Journal of investigative dermatology.

[4]  T. Franz.  On the bioavailability of topical formulations of clindamycin hydrochloride. , 1983, Journal of the American Academy of Dermatology.

[5]  L. Roza,et al.  Percutaneous Absorption of Mexoryl SX® in Human Volunteers: Comparison with in vitro Data , 2003, Skin Pharmacology and Physiology.

[6]  J. Hadgraft,et al.  THE ROLE OF VEHICLES IN THE PERCUTANEOUS ABSORPTION OF CORTICOSTEROIDS. , 1965, The British journal of dermatology.

[7]  T. Auton,et al.  Pharmacokinetics of Fluazifop-butyl in Human Volunteers II: Dermal Dosing , 1992, Human & experimental toxicology.

[8]  H. Maibach,et al.  Percutaneous penetration of steroids in man. , 1969, The Journal of investigative dermatology.

[9]  J. Cocker,et al.  Oral and dermal absorption of chlorpyrifos: a human volunteer study. , 1999, Occupational and environmental medicine.

[10]  J. Caldwell,et al.  Percutaneous absorption of nicotinic acid, phenol, benzoic acid and triclopyr butoxyethyl ester through rat and human skin in vitro: further validation of an in vitro model by comparison with in vivo data. , 1992, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[11]  T. Franz,et al.  Vehicle effects on percutaneous absorption: in vivo and in vitro comparisons with human skin , 1986, The British journal of dermatology.

[12]  Robert L. Bronaugh.  Methods for in Vitro Percutaneous Absorption , 1995 .

[13]  H. Maibach,et al.  Percutaneous absorption of diazinon in humans. , 1993, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[14]  R. Guy,et al.  Percutaneous Penetration and Mass Balance Accountability: Technique and Implications for Dermatology , 1989 .

[15]  P Sartorelli,et al.  In vitro predictions of skin absorption of caffeine, testosterone, and benzoic acid: a multi-centre comparison study. , 2004, Regulatory toxicology and pharmacology : RTP.

[16]  T. Franz.  Percutaneous absorption on the relevance of in vitro data. , 1975, The Journal of investigative dermatology.

[17]  R A Ford,et al.  The in vivo dermal absorption and metabolism of [4-14C] coumarin by rats and by human volunteers under simulated conditions of use in fragrances. , 2001, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[18]  T. Franz.  The finite dose technique as a valid in vitro model for the study of percutaneous absorption in man. , 1978, Current problems in dermatology.

[19]  H. Maibach,et al.  In vivo percutaneous absorption of boric acid, borax, and disodium octaborate tetrahydrate in humans compared to in vitro absorption in human skin from infinite and finite doses. , 1998, Toxicological sciences : an official journal of the Society of Toxicology.

[20]  P. Blain,et al.  The percutaneous absorption and skin distribution of lindane in man. II. In vitro studies. , 1997, Human & experimental toxicology.

[21]  J. M. Perkins,et al.  Oral and Dermal Pharmacokinetics of Triclopyr in Human Volunteers , 1989, Human toxicology.

[22]  R. Guy,et al.  Bioavailability of topically administered steroids: a "mass balance" technique. , 1988, The Journal of investigative dermatology.

[23]  D. Sauder,et al.  In vitro and in vivo percutaneous absorption of 14C-chloroform in humans , 1995, Human & experimental toxicology.

[24]  R. Guy,et al.  Methods for Assessing Percutaneous Absorption , 1996 .

[25]  J. J. van de Sandt,et al.  Comparative in vitro-in vivo percutaneous penetration of the fungicide ortho-phenylphenol. , 2002, Regulatory toxicology and pharmacology : RTP.

[26]  Robert M. Deiters.  Organization for Economic Co-Operation and Development (OECD). , 1968 .

[27]  T. Franz,et al.  Comparative percutaneous absorption of lindane and permethrin. , 1996, Archives of dermatology.

[28]  P. Blain,et al.  The percutaneous absorption and skin distribution of lindane in man , 1997, Human & experimental toxicology.

[29]  J. Hadgraft,et al.  The influence of vehicles on skin penetration , 1964, The Journal of pharmacy and pharmacology.

[30]  G. Nohynek,et al.  Human systemic exposure to a [14C]-para-phenylenediamine-containing oxidative hair dye and correlation with in vitro percutaneous absorption in human or pig skin. , 2004, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[31]  H I Maibach,et al.  Percutaneous absorption of nitroaromatic compounds: in vivo and in vitro studies in the human and monkey. , 1985, The Journal of investigative dermatology.

[32]  H. Maibach,et al.  Absorption of some organic compounds through the skin in man. , 1970, The Journal of investigative dermatology.

[33]  H. Macfarland.  Applied toxicology of petroleum hydrocarbons , 1984 .

[34]  H. Maibach,et al.  In vivo percutaneous absorption of benzene in man: forearm and palm. , 2008, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[35]  H I Maibach,et al.  In vivo and in vitro percutaneous absorption and skin evaporation of isofenphos in man. , 1992, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[36]  J. J. van de Sandt,et al.  Comparative in vitro-in vivo percutaneous absorption of the pesticide propoxur. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[37]  T. Higuchi,et al.  Enhancement of percutaneous absorption by the use of volatile: nonvolatile systems as vehicles. , 1969, Journal of Pharmacy and Science.

[38]  S. Hotchkiss,et al.  Comparative in vitro skin absorption and metabolism of coumarin (1,2-benzopyrone) in human, rat, and mouse. , 1997, Toxicology and applied pharmacology.

[39]  J. Ostrenga,et al.  Significance of vehicle composition. II. Prediction of optimal vehicle composition. , 1971, Journal of pharmaceutical sciences.

[40]  J. Ostrenga,et al.  Significance of vehicle composition. I. Relationship between topical vehicle composition, skin penetrability, and clinical efficacy. , 1971, Journal of pharmaceutical sciences.