Pharmacokinetic evaluation of labelled sertaconazole after dermal application.
14C-labelled 7-chloro-3-[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy-methyl] benzo[b]thiophene (sertaconazole, FI-7045, CAS 99592-32-2) was administered systemically (i.v. route) and topically (dermal route) in different formulations at doses of 10 mg/kg to hairless Sprague-Dawley rats. Determination of plasma and liver levels of radioactivity demonstrated that the dermal application of sertaconazole induced very low systemic absorption with all the formulations used: 1.47% for sertaconazole cream, 1.97% for sertaconazole solution, 0.665% for sertaconazole powder and 0.885% for sertaconazole gel. Calculations were made from the areas under plasma levels curves of each topical administration in comparison with intravenous administration. Significant radioactivity levels were found in the liver, which was consistent with a high hepatic metabolization and faecal excretion of the substance. However, the liver levels after topical application were virtually insignificant in comparison with the levels in the same organ obtained after intravenous administration.
Agut
J
J
Research Centre, Ferrer Group, Barcelona, Spain.
Moren
M
M
Rego
M
M
Sacristán
A
A
Ortiz
J A
JA
D000287:Administration, Topical; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D005260:Female; D005782:Gels; D007093:Imidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013876:Thiophenes / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000935:Antifungal Agents; D005782:Gels; D007093:Imidazoles; D013876:Thiophenes; C061131:sertaconazole