Tissue distribution of terbinafine in rats

✍ Scribed by Mahboubeh Hosseini-Yeganeh; Andrew J. McLachlan

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 217 KB
• Volume: 90
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.1132

✦ Synopsis

Terbina®ne is an allylamine antifungal agent that is highly lipophilic and keratophilic. The aim of this study was to investigate terbina®ne distribution in peripheral and visceral tissues after intravenous administration to rats. Terbina®ne, 6 mg/kg, was administered to 33 male Sprague-Dawley rats via a jugular vein cannula over 30 s. Groups of 3 rats were sacri®ced at each of 11 time points (up to 24 h), and plasma and tissues were dissected, sampled, and analyzed by high-performance liquid chromatography. Terbina®ne plasma concentrations declined in a triexponential fashion, with an estimated elimination half-life of 10 h. The estimated clearance of terbina®ne in rats was 2 L/h/kg and the volume of distribution at steady state was 6 L/ kg. The tissue-to-plasma partition coef®cient (K p ) of terbina®ne for different tissues was calculated using the ratio of the area under the curve of concentration±time for tissues (AUC tissue ) to that for plasma (AUC plasma ), by parametric and semiparametric approaches. There was good agreement between K p estimates determined by different approaches. The preferential distribution of terbina®ne to adipose and skin (K p 49 and 45, respectively) was consistent with the lipophilicity of the drug. Uptake of terbina®ne into brain (K p 1.3) and muscle (K p 1.0) was signi®cantly lower. In conclusion, terbina®ne displays extensive uptake to peripheral tissues, which contributes to the long elimination half-life of this drug.