Pharmacokinetics of cutaneous Sulconazole nitrate in the hairless rat: absorption, excretion, tissue concentrations.
After cutaneous application of radioactive solutions of Sulconazole nitrate in the hairless rat, the total absorption of the substance by the skin, estimated from the sum of the cumulative urinary and fecal excretions over 96 h, was 2.4% of the dose administered. The elimination reached a maximum between 6 and 24 h and was virtually complete after 96 h. The excretion was almost equally distributed between the urine and the feces, which corresponds to an intense elimination via the biliary tract. The quantities present in the stratum corneum, epidermis and dermis at the end of the period of contact constituted another estimation of the total absorption of the substance which confirmed the previous estimation (3.6% of the dose). The measurement of the concentrations of Sulconazole and its metabolites in the various layers of the skin revealed a high affinity of the substance for the stratum corneum, where it remained present in large quantities for more than 48 h. This affinity is due to the very intense lipophilia of the molecule. The concentrations in the other tissues were inversely proportional to the distance from the surface of the skin and were virtually nil in the circulating blood. These results suggest the absence of risk of systemic effects after cutaneous administration of Sulconazole and support the recommended therapeutic protocol in man (one administration per day).
Hercelin
B
B
Laboratories Cassenne, Osny, France.
Delaunay-Vantrou
M
M
Alamichel
F
F
Mazza
M
M
Marty
J P
JP
D000279:Administration, Cutaneous; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics* / Q000652:urine; D004817:Epidermis / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D051381:Rats; D011923:Rats, Nude / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D014018:Tissue Distribution; D014316:Tritium
D000935:Antifungal Agents; D007093:Imidazoles; D014316:Tritium; C033308:sulconazole