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Titolo:
CUTANEOUS METABOLISM OF NITROGLYCERIN INVITRO .2. EFFECTS OF SKIN CONDITION AND PENETRATION ENHANCEMENT
Autore:
HIGO N; HINZ RS; LAU DTW; BENET LZ; GUY RH;
Indirizzi:
UNIV CALIF SAN FRANCISCO,SCH PHARM,DEPT PHARM SAN FRANCISCO CA 94143 HISAMITSU PHARMACEUT CO INC TOSU SAGA 841 JAPAN UNIV CALIF SAN FRANCISCO,DEPT PHARMACEUT CHEM SAN FRANCISCO CA 94143
Titolo Testata:
Pharmaceutical research
fascicolo: 3, volume: 9, anno: 1992,
pagine: 303 - 306
SICI:
0724-8741(1992)9:3<303:CMONI.>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
HAIRLESS MOUSE SKIN; PERCUTANEOUS-ABSORPTION;
Keywords:
NITROGLYCERIN; CUTANEOUS METABOLISM; TRANSPORT; PENETRATION ENHANCER; AZONE;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
10
Recensione:
Indirizzi per estratti:
Citazione:
N. Higo et al., "CUTANEOUS METABOLISM OF NITROGLYCERIN INVITRO .2. EFFECTS OF SKIN CONDITION AND PENETRATION ENHANCEMENT", Pharmaceutical research, 9(3), 1992, pp. 303-306

Abstract

The effects of skin storage. skin preparation, skin pretreatment witha penetration enhancer, and skin barrier removal by adhesive tape-stripping on the concurrent cutaneous transport and metabolism of nitroglycerin (GTN) have been studied in vitro using hairless mouse skin. Storing the skin for 10 days at 4-degrees-C did not alter barrier function to total nitrate flux [GTN + 1.2-glyceryl dinitrate (1,2-GDN) + 1,3-glyceryl dinitrate (1,3-GDN)]. However, metabolic function was significantly impaired and suggested at least fivefold loss of enzyme activity. Heating skin to 100-degrees-C for 5 min appreciably damaged hairless mouse skin barrier function. The ability to hydrolyze GTN was still present, however, and remained constant over the 10-hr experimental period, in contrast to the "control," which showed progressively decreasing enzymatic function with time. Pretreatment of hairless mouse skin in vivo (prior to animal sacrifice, tissue excision, and in vitro transport/metabolism studies) with 1-dodecylazacycloheptan-2-one (Azone), a putative penetration enhancer, significantly lowered the skin barrier to nitrate flux (relative to the appropriate control). Again, barrier perturbation resulted in essentially constant metabolic activity over the observation period. The ratio of metabolites formed (1,2-GDN/1,3-GDN) was increased from less than unity to slightly above 1 by the Azone treatment. Adhesive tape-stripping gradually destroyed skin barrier function by removal of the stratum corneum. The effects of 15 tape-strips were identical to those of Azone pretreatment: a greatly enhanced flux, a constant percentage formation of metabolites over 10 hr (once again), and an increase in the 1,2-GDN/1,3 GDN ratio. Overall, the experiments caution that, for transdermal drug delivery candidates susceptible to skin metabolism, the status of barrier function (enhancer pretreated, skin damage or disease, etc.) may significantly affect systemic availability.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/08/20 alle ore 14:33:48