Homeostatic equilibrium of L-carnitine family before and after i.v. administration of propionyl-L-carnitine in humans, dogs and rats.
Propionyl-L-carnitine is a minor component of L-carnitine family which, when exogenously administered, proved to possess interesting cardiovascular activities. In this paper the pharmacokinetics of propionyl-L-carnitine was investigated in humans, dogs and rats after intravenous administration. In all the three species the base homeostatic equilibrium was carefully investigated in plasma and in urine during the 24 h period before the administration. Propionyl-L-carnitine, acetyl-L-carnitine, L-carnitine and total acid soluble L-sensitive were assayed in plasma and urine with very sensitive enantioselective radioenzyme assay. After dosing propionyl-L-carnitine rapidly increased, and then decreased reaching the base value within 6 h or more, depending on the species and the dose. Also L-carnitine in all the three species and acetyl-L-carnitine in rats and dogs increased, but the increase was more sustained when compared to propionyl-L-carnitine. Urinary excretion paralleled plasma concentration, reaching the highest value in the 24 h-period after dosing. Renal clearance also increased reflecting the behaviour of plasma concentration and urinary excretion. Results obtained all the conclusion that two homeostatic equilibrium of L-carnitine family components, namely the inter-exchange between L-carnitine and its esters catalyzed by carnitine acyl transferases, and a saturable tubular reabsorption process with differentiated threshold for each component.
Marzo
A
A
Department of Drug Metabolism and Pharmacokinetics Sigma-Tau S.p.A., Rome, Italy.
Cardace
G
G
Corbelleta
C
C
Bassani
E
E
Morabito
E
E
Arrigoni Martelli
E
E
D000108:Acetylcarnitine / Q000493:pharmacokinetics; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics; D004285:Dogs; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism
C003223:propionylcarnitine; D000108:Acetylcarnitine; D002331:Carnitine