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PHARMACOKINETICS

Disposition and Metabolite Kinetics of Oral L-carnitine in Humans

Marcus A. Bain, Robert W. Milne, PhD and Allan M. Evans, PhD

From the Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Australia.

The pharmacokinetics of L-carnitine and its metabolites were investigated in 7 healthy subjects following the oral administration of 0, 0.5, 1, and 2 g 3 times a day for 7 days. Mean plasma concentrations of L-carnitine across an 8-hour dose interval increased significantly (P < .05) from a baseline of 54.2 ± 9.3 µM to 80.5 ± 12.5 µM following the 0.5-g dose; there was no further increase at higher doses. There was a significant increase (P < .001) in the renal clearance of L-carnitine indicating saturation of tubular reabsorption. Trimethylamine plasma levels increased proportionately with L-carnitine dose, but there was no change in renal clearance. A significant increase in the plasma concentrations of trimethylamine-N-oxide from baseline was evident only for the 2-g dose of L-carnitine (from 34.5 ± 2.0 to 149 ± 145 µM), and its renal clearance decreased with increasing dose (P < .05). There was no evidence for nonlinearity in the metabolism of trimethylamine to trimethylamine-N-oxide. In conclusion, the pharmacokinetics of oral L-carnitine display nonlinearity above a dose of 0.5 g 3 times a day.

Key Words: L-carnitine • trimethylamine • trimethylamine-N-oxide • gas chromatography • N-nitrosodimethylamine

Address for reprints: Allan M. Evans, PhD, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000; e-mail: allan.evans{at}unisa.edu.au.


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