Pharmacokinetics of Drugs in Blood II. Unusual Distribution and Storage Effect of Furosemide

Furosemide was found to exhibit both in vitro and in vivo unusual distribution kinetics in whole blood. For example, at an initial blood concentration of 10 microgram/ml, a 'trough' plasma level phenomenon occurring at 5 min was found in the in vitro study using blood from humans, rabbits, and dogs. A similar effect was also observed in rabbits following intravenous dosing. The effect of the time elapsed between blood collection and centrifugation on the measured plasma level, the so called 'blood storage effect' was clearly demonstrated in rabbit studies. A difference of up to 32% was found. Furosemide was found to be stable in blood, and the equilibrium plasma/blood cell concentration ratios were about 1.5-2.0 at 0.1-50 micrograms/ml in blood.