Disposition of L-carnitine and its short-chain esters, acetyl-L-carnitine and propionyl-L-carnitine, in the rat isolated perfused liver

L-Carnitine (LC)1 is an endogenous compound that facilitates the transport of long-chain fatty acids into the mitochondrial matrix for b-oxidation (Bremer, 1983; Rebouche and Paulson, 1986; Bahal and Bressler, 1987). In mammals, LC can be absorbed from dietary sources but also synthesized, primarily in the liver, from L-lysine and L-methionine (Bohmer, 1974; Hoppel and Davis, 1986). LC is administered clinically for the treatment of primary and secondary carnitine deficiency syndromes. Short-chain carnitine esters, such as acetyl-Lcarnitine (ALC) and propionyl-L-carnitine (PLC), are produced by esterification of the hydroxyl group of LC and form components of the endogenous carnitine pools in humans and experimental animals. ALC supplementation has been reported to reduce the progression of Alzheimer’s disease (Bowman, 1992), and patients with intermittent claudication exhibited improved walking capacity after the administration of PLC (Brevetti et al., 1995). Studies comparing the pharmacokinetics of LC after oral and intravenous administration demonstrate that the absolute bioavailability of the compound is less than 20% (Harper et al., 1988; Sahajwalla et al., 1995). Although there are no published data on the oral bioavailability of ALC and PLC, data from studies in both humans and experimental animals suggest that, like LC, both esters have a low bioavailability (,20%) after oral administration (A. Longo, unpublished observations).