EXCRETION AND METABOLISM OF PROPIONYL-L-CARNITINE IN THE ISOLATED-PERFUSED RAT-KIDNEY

Propionyl-L-carnitine (PLC) is an ester of L-carnitine (LC) under eval uation for the treatment of cardiovascular disorders. The renal dispos ition of PLC was studied in the isolated perfused rat kidney with deut erium-labeled derivative (PLC-CD3). Kidneys of male Sprague-Dawley rat s were perfused at initial PLC-CD3 concentrations of 10 (n = 4) and 20 0 mu M (n = 5). High-performance liquid chromatography/mass spectromet ry was used to quantify PLC-CD3, deuterated L-carnitine (LC-CD3) and a cetyl-L-carnitine (ALC-CD3) in perfusate and urine. PLC-CD3 in perfusa te decreased in a monoexponential manner with a half-life of 90 +/- 24 min (S.D.) (10 mu M) and 94 +/- 11 min (200 mu M). The renal excretor y clearance of PLC-CD3 was significantly lower (P < .05, unpaired t te st) at an initial concentration of 10 mu M (45 +/- 23 mu l/min) than a t 200 mu M (85 +/- 28 mu l/min), but in both cases it was substantiall y less than the glomerular filtration rate, which indicates extensive tubular reabsorption. The renal excretory clearance of PLC-CD3 represe nted less than 6% of the total clearance, which suggests that metaboli sm is the major renal elimination route for this compound. The appeara nce in perfusate and urine of LC-CD3 and ALC-CD3 provided additional e vidence for a metabolic role of the kidney. The apparent renal excreto ry clearance values for these metabolites were always significantly hi gher than the values obtained for the corresponding endogenous compoun ds, which suggests that LC-CD3 and ALC-CD3, as formed metabolites, und erwent passive or carrier-mediated movement directly into urine.