PLASMA-CLEARANCE OF CHOLYL-LYSYL-FLUORESCEIN - A PILOT-STUDY IN HUMANS

Background/Aims: Cholyl-lysyl-fluorescein is a fluorescent analogue of the natural bile acid, cholyl glycine, In vivo and in vitro studies s howed that this analogue has many biological characteristics similar t o cholyl glycine. In this study we analysed cholyl-lysyl-fluorescein p lasma clearance in sis healthy volunteers as a potential quantitative liver function test, Methods: The compound in water for injection was administered as an i.v. bolus in the dose of 0.02 mg/kg b.w. Results: The plasma elimination curve showed rapid, intermediate and slow phase s of clearance, Half-life (T-1/2 time) for the first (t(1/2 1st phase) ), second (t(1/2 2nd phase)) and third (t(1/2 3rd phase)) phases of el imination was 1.7+/-0.9 min, 6.7+/-1.6 min and 68+/-17 min, respective ly, Ninety-minute plasma retention (% dose/I plasma) was 2.2%, Cholyl- lysyl-fluorescein volume of distribution and residual fluorescence aft er 60 min were similar to the data obtained by others for natural or r adiolabelled bile acids. In five out of sis healthy volunteers a 25-fo ld higher dose of cholyl-lysyl-fluorescein (0.5 mg/kg b.w.) was inject ed to estimate the safety margins of the compound, This dose was elimi nated at a disappearance rate similar to that of the dose of 0.02 mg/k g b.w. and did not cause any adverse reactions, Serum liver tests meas ured before and after injection did not change significantly. Conclusi ons: This study showed that cholyl-lysyl-fluorescein clearance is simi lar to the clearance of endogenous natural bile acids and may potentia lly offer a new, dynamic test of liver function.