Studies on the Metabolic Fate of Neticonazole (III):Absorption, Distribution and Excretion in Rats and Guinea Pigs after a Single Dermal Application

• Published in: Drug Metabolism and Pharmacokinetics Vol. 6; no. 4; pp. 553 - 566
• Main Authors: YATABE, Naomi, UEDA, Takao, ESUMI, Yoshio, NAGAI, Tamotsu, HANAWA, Sinya, IWASA, Akira, TAKAICHI, Matsuo, YANO, Kenichi, NUMATA, Hiroshi, MITSUGI, Kouichi
• Format: Journal Article
• Language: English
• Published: The Japanese Society for the Study of Xenobiotics 1991
• Subjects: absorption; dermal application; distribution; excretion; guinea pig; neticonazole (SS717); rat
• ISSN: 0916-1139
• DOI: 10.2133/dmpk.6.553

The absorption, distribution and excretion of 14C-neticonazole(14C-SS717), a new imidazole antimycotic, were studied in male rats and guinea pigs after dermal application of the drug as cream or solution formulations. 1. After dermal application (25mg SS717/2.5g cream/kg) of 14C-SS717 cream formulation in rats, the blood concentration of radioactivity reached the maximum level (30.0ng equiv. of SS717/ml) at 24hr, and the elimination half-life at the terminal phase was 97hr. The cumulative urinary and fecal excretions of radioactivity were 3.8 and 1.8% of applied dose during 120hr in rats after dermal application of 14C-SS717 cream formulation. 2. After dermal application (25mg SS717/2.5ml solution/kg) of 14C-SS717 solution formulation in rats, the blood level of radioactivity reached the maximum level (55.8 ?? 65.0ng equiv. of SS717/ml) at 8 ?? 32hr, and the elimination half-life at the terminal phase was 71hr. The cumulative urinary and fecal excretions of radioactivity were 3.6 and 1.7% of the dose during 120hr in rats after dermal application of 14C-SS717 solution formulation. 3. Microautoradiograms of dorsal skin after application of 14C-SS717 cream or solution(10 mg SS717/lg cream or 1ml solution/body) in guinea pigs suggested that 14C-SS717 distributed mainly into the stratum corneum following absorption via the transepidermal route, or partial absorption through the transfollicular route.4. Whole body antoradiograms demonstrated a high levels of radioactivity in the skin, at the application site and, in the intestinal content, bile, gastric content, in the urine presented in urinary bladder, liver, kidney and lung. No difference between these two preparations was observed in the distribution pattern of radiactivity.