期刊
JOURNAL OF CLINICAL PHARMACOLOGY
卷 46, 期 10, 页码 1163-1170出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0091270006292851
关键词
L-carnitine; trimethylamine; trimethylamine-N-oxide; gas chromatography; N-nitrosodimethylamine
The phormacokinetics 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 mu M to 80.5 +/- 12.5 mu M 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 mu M), 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.
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