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Pharmacokinetics of L-Carnitine

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Abstract

L-Carnitine is a naturally occurring compound that facilitates the transport of fatty acids into mitochondria for β-oxidation. Exogenous L-carnitine is used clinically for the treatment of carnitine deficiency disorders and a range of other conditions.

In humans, the endogenous carnitine pool, which comprises free L-carnitine and a range of short-, medium- and long-chain esters, is maintained by absorption of L-carnitine from dietary sources, biosynthesis within the body and extensive renal tubular reabsorption from glomerular filtrate. In addition, carrier-mediated transport ensures high tissue-to-plasma concentration ratios in tissues that depend critically on fatty acid oxidation. The absorption of L-carnitine after oral administration occurs partly via carrier-mediated transport and partly by passive diffusion. After oral doses of 1–6g, the absolute bioavailability is 5–18%. In contrast, the bioavailability of dietary L-carnitine may be as high as 75%. Therefore, pharmacological or supplemental doses of L-carnitine are absorbed less efficiently than the relatively smaller amounts present within a normal diet.

L-Carnitine and its short-chain esters do not bind to plasma proteins and, although blood cells contain L-carnitine, the rate of distribution between erythrocytes and plasma is extremely slow in whole blood. After intravenous administration, the initial distribution volume of L-carnitine is typically about 0.2–0.3 L/kg, which corresponds to extracellular fluid volume. There are at least three distinct pharmacokinetic compartments for L-carnitine, with the slowest equilibrating pool comprising skeletal and cardiac muscle.

L-Carnitine is eliminated from the body mainly via urinary excretion. Under baseline conditions, the renal clearance of L-carnitine (1–3 mL/min) is substantially less than glomerular filtration rate (GFR), indicating extensive (98–99%) tubular reabsorption. The threshold concentration for tubular reabsorption (above which the fractional reabsorption begins to decline) is about 40–60 µmol/L, which is similar to the endogenous plasma L-carnitine level. Therefore, the renal clearance of L-carnitine increases after exogenous administration, approaching GFR after high intravenous doses.

Patients with primary carnitine deficiency display alterations in the renal handling of L-carnitine and/or the transport of the compound into muscle tissue. Similarly, many forms of secondary carnitine deficiency, including some drug-induced disorders, arise from impaired renal tubular reabsorption. Patients with end-stage renal disease undergoing dialysis can develop a secondary carnitine deficiency due to the unrestricted loss of L-carnitine through the dialyser, and L-carnitine has been used for treatment of some patients during long-term haemodialysis. Recent studies have started to shed light on the pharmacokinetics of L-carnitine when used in haemodialysis patients.

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Acknowledgements

The authors would like to thank Ms Wave Sewlall, Ms Lauren Graham and Ms Judy Inge for their expert assistance in the preparation of this manuscript. There were no sources of funding or conflicts of interest directly relevant to the content of this review.

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  1. Centre for Pharmaceutical Research, School of Pharmaceutical, Molecular and Biomedical Sciences, University of South Australia, North Terrace, Adelaide, South Australia, 5000, Australia

    Allan M. Evans

  2. Sigma-Tau Pharmaceuticals Inc, Gaithersburg, Maryland, USA

    Gianfranco Fornasini

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Correspondence to Allan M. Evans.

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Evans, A.M., Fornasini, G. Pharmacokinetics of L-Carnitine. Clin Pharmacokinet 42, 941–967 (2003). https://doi.org/10.2165/00003088-200342110-00002

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