Percutaneous penetration of nicotinates: in vivo and in vitro measurements.
Guy-RH; Carlstrom-EM; Bucks-DA; Hinz-RS; Maibach-HI
J Pharm Sci 1986 Oct; 75(10):968-972
The percutaneous penetration of nicotinates was studied in-vivo and in-vitro. In-vitro, the ability of carbon-14 (C14) labeled nicotinic-acid (59676), methyl-nicotinate (93607), ethyl-nicotinate (614186), hexyl-nicotinate (23597822), or benzyl-nicotinate (94440) to penetrate through skin removed from the backs of hairless mice mounted on glass diffusion cells was evaluated. In some experiments the skin had been stripped of its stratum-corneum barrier. In-vivo, C14 labeled methyl-nicotinate, ethyl-nicotinate, hexyl-nicotinate, or benzyl-nicotinate was applied to the forearm of human volunteers. The extent of absorption was determined by collecting urine samples at various times over the next 5 days and analyzing them for C14 activity. The octanol/water partition coefficients of the compounds were determined experimentally or obtained from the literature. In- vitro, 80 to 90 percent of the polar compounds, methyl-nicotinate and ethyl-nicotinate, rapidly penetrated the skin. The less polar compounds, hexyl-nicotinate and benzyl-nicotinate, penetrated very slowly. Nicotinate showed very little penetration, even after 50 hours. Nicotinic-acid, methyl-nicotinate, and benzyl-nicotinate penetrated skin with the stratum-corneum removed with equal efficiency. The in-vivo data could be fit to a four compartment pharmacokinetic model consisting of the stratum-corneum, viable epidermis, blood, and urine. The ratios of the rate constants in the model correlated acceptably with the partition coefficients of the compounds. The authors conclude that in mouse skin methyl- nicotinate and ethyl-nicotinate can effectively bypass the stratum- corneum barrier, whereas nicotinic-acid and the other compounds cannot. Skin transport is the rate limiting step in the skin absorption of these compounds. In human skin the nicotinates apparently have a higher affinity for the stratum-corneum than for viable tissue.
NIOSH-Publication; NIOSH-Grant; Dermatitis; In-vitro-studies; Humans; In-vivo-studies; Radiobiology; Skin-absorption; Urinalysis; Organo-nitrogen-compounds; Esters; Pharmacodynamics
Pharmacy University of California 926 Medical Sciences Building San Francisco, Calif 94143
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Journal of Pharmaceutical Sciences
University of California San Francisco, San Francisco, California