Methyl nicotinate, percutaneous

Bartek MJ, LaBudde JA (1975) Percutaneous absorption in vitro. In Maibach HI (ed) Animal Models in Dermatology. Churchill Livingstone, New York, pp 103-120 Bronaugh R, Maibach HI (1999) Percutaneous Absorption. 3rd edn. Marcel Dekker, New York and 4thedn in press Guy RH, Wester RC, Tur E, Maibach HI (1983) Noninvasive assessments of the percutaneous absorption of methyl nicoti-nate in humans. J Pharm Sci 72(9) 1077-1079 Guy RH, Tur E, Bugatto B et al. (1984) Pharmaco-dynamic measurements of methyl nicotinate percutaneous absorption. Pharm Res 1 76-81... 

Issachar, N., Gall, Y., Borrel, M.T., and Poelman, M.-C., Correlation between percutaneous penetration of methyl nicotinate and sensitive skin, using laser Doppler imaging. 

Tur, E. Maibach, H.I. Guy, R.H. Percutaneous penetration of methyl nicotinate at three anatomic sites evidence for an appendageal contribution to transport Skin Pharmacol. 1991, 4, 230-234. 

Ashton P, Walters KA, Brain KR, Hadgraft J. Surfactant effects in percutaneous absorption. Part 1. Effects on the transdermal flux of methyl nicotinate. Int J Pharm 1992 87(10) 261—264. 

The effect of age on percutaneous absorption has been examined in vivo in man with variable results. It was postulated (Roskos et al. 1989) that reduced hydration levels and lipid content of older skin may be responsible for a demonstrated reduction in skin permeability where the permeants were hydrophilic in nature (no reduction was seen for model hydrophobic compounds) (Table 14.2). The reduced absorption of benzoic acid demonstrated in the elderly (Rougier 1991) was in line with this suggestion, but not the reduction in absorption of testosterone (lipophilic) (Roskos et al. 1986), or lack of change in the absorption of methyl nicotinate (more hydrophilic) with age (Guy et al. 1983). There are a number of potential physiological changes which may be responsible for age-related alterations, including an increase in the size of individual stratum corneum corneocytes, increased dehydration of the outer layers of the stratum corneum with age, decreased epidermal turnover and decreased microvascular clearance (reviewed in Roskos and Maibach 1992). The issue of age-related variability, however, is far from resolved. 

Boelsma, E, Anderson, C., Karlsson, A.M., and Ponec, M., 2000, Microdialysis technique as a method to study the percutaneous penetration of methyl nicotinate through excised human skin, reconstructed epidermis, and human skin in vivo, Pharm. Res., 17, 141-147. 

One of the earlier studies demonstrating the role of blood flow on percutaneous absorption in humans used comparison dermal concentrations after topical application in vitro and in vivo (Schaefer and Stuttgen, 1978). Perfusion caused by cutaneous microcirculation also affected responses after the topical penetration of the vasodilator methyl nicotinate in humans (Guy et al., 1983). Altered transdermal drug absorption of the vasoactive nonsteroidal antiinflammatory drug (NSAID) methyl salicylate (MeSA) has also been attributed to changes in in vivo cutaneous perfusion. Exercise, heat exposure, or both increased MeSA absorption more than three times the control levels in six volunteers (Danon etal., 1986). A later case study reported that skin necrosis and other toxic symptoms occurred when a heating pad was used with a topical MeSA and menthol formulation meant to treat arthritic pain (Heng, 1987). 

Gorsline, J. Okerholm, R.A. Rolf, C.N. Moos, C.D. Hwang, S.S. Comparison of plasma nicotine concentrations after application of nicoderm (nicotine transdermal system) to different skin sites. J. Clin. Pharmacol. 1992,32, 576-581. Wester, R.C. Maibach, H.I. Bucks, D.A.W. In vivo percutaneous absorption of paraquat from hand, leg and forearm of humans. J. Toxicol. Environ. Health 1984, 14, 759-762. Taskovich, L. Shaw, J.E. Regional differences in the morphology of human skin correlation with variations in drug permeability. J. Invest. Dermatol. 1978, 70, 111. Roberts, M.S. Eavretto, W.A. Meyer, A. Reckmann, M. Wongseelashote, T. Topical bioavailability of methyl sahcy-late. Aust. N.Z. J. Med. 1982, 12, 303-305. 

The kinetic model has been used to analyze percutaneous penetration rate data for nine molecules aspirin, benzoic acid, caffeine, chloramphenicol, dlethyltoluamlde, nitrobenzene, salicylic acid ( ) and the methyl and benzyl esters of nicotinic acid ( 9 ). Experimentally, the chemicals ( C-labelled) were applied topically In acetone to the ventral forearm of human volunteers and the urinary excretion of radioactivity was then measured over a five day period ... 

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