Skin blister fluid--an access to the peripheral compartment. Implications of a study on the behaviour of bendroflumethiazide in rats

Abstract

Pharmacokinetics of bendroflumethiazide (bft) were investigated in blood and skin suction blister fluid (SBF) in rats dosed 10 mg/kg intravenously. Additionally tissue levels were determined. Mean volume of skin blisters amounted to 10 or 20 microliters, respectively. While blood levels were best described according to a three-compartment model (terminal half-life 152 min) bft concentrations in SBF raised to a maximum 60 min post administration and thereafter declined (half-life 143 min). There was no significant effect of blister volume on SBF level-time course. A close relation between bft concentrations in SBF and the calculated amount of drug in the deep compartment was observed (r = 0.987). Plasma protein binding of bft was 84% while binding to SBF amounted to 76%. The drug is evenly distributed between plasma and erythrocytes. Therefore concentrations of unbound drug in SBF exceed those in plasma during the terminal phase. The determination of tissue levels showed bft concentrations in liver, kidney, lung and heart to follow blood levels whereas the pharmacokinetic behaviour of skin and muscle is rather close to that of the deep compartment. The results suggest the determination of skin blister fluid levels to be valuable if a drug acts from the tissue compartment then SBF being closer to the biophase than blood.