Onset and offset pharmacodynamics of propofol.

Propofol whole blood and plasma concentrations at offset of hypnosis in eighteen patients were inversely related to patient age and body fat. The relationship between propofol concentrations and body fat is derived from the relationship between age and body fat and age was the single independent predictor of concentrations at offset of propofol hypnosis.

Tissue distribution of terbinafine in rats.

Terbinafine is an allylamine antifungal agent that is highly lipophilic and keratophilic. The aim of this study was to investigate terbinafine distribution in peripheral and visceral tissues after intravenous administration to rats. Terbinafine, 6 mg/kg, was administered to 33 male Sprague-Dawley rats via a jugular vein cannula over 30 s. Groups of 3 rats were sacrificed at each of 11 time points (up to 24 h), and plasma and tissues were dissected, sampled, and analyzed by high-performance liquid chromatography. Terbinafine plasma concentrations declined in a triexponential fashion, with an estimated elimination half-life of 10 h. The estimated clearance of terbinafine in rats was 2 L/h/kg and the volume of distribution at steady state was 6 L/kg. The tissue-to-plasma partition coefficient (K(p)) of terbinafine 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 terbinafine to adipose and skin (K(p) = 49 and 45, respectively) was consistent with the lipophilicity of the drug. Uptake of terbinafine into brain (K(p) = 1.3) and muscle (K(p) = 1.0) was significantly lower. In conclusion, terbinafine displays extensive uptake to peripheral tissues, which contributes to the long elimination half-life of this drug.