Oral L-carnitine: metabolite formation and hemodialysis.
L-Carnitine has important roles in intermediary metabolism and patients with end-stage renal disease who are undergoing hemodialysis may develop a secondary L-carnitine deficiency. The extent of accumulation of the metabolites trimethylamine and trimethylamine-N-oxide when L-carnitine is administered orally has not been investigated previously in this population. Oral L-carnitine at a dose of 1 g daily was administered for twelve days to six patients with end-stage renal disease undergoing hemodialysis thrice weekly. Pre-dialysis plasma concentrations of L-carnitine (mean +/- SD) increased significantly (P < 0.05) from day 1 (baseline; 32.4 +/- 6.1 microM) to day 8 (66.1 +/- 13.8 microM) remaining constant thereafter. Although plasma levels of trimethylamine remained unaltered, the pre-dialysis plasma concentrations of trimethylamine-N-oxide increased significantly (P < 0.05) from day 1 (289.1 +/- 236.1 microM) to day 12 (529.0 +/- 237.9 microM). The hemodialysis clearances for L-carnitine, trimethylamine and trimethylamine-N-oxide were 14.3 +/- 8.2, 14.1 +/- 10.6 and 12.4 +/- 5.4 L/h, respectively, indicating their efficient removal by dialysis. Oral administration of L-carnitine at a dose of 1 g daily increases plasma concentrations of this substance to physiological levels in patients with end-stage renal disease who are undergoing hemodialysis. However, concerns about the possible deleterious consequences of such a dosage regimen still remain given that plasma concentrations of trimethylamine-N-oxide were continually rising and approximately doubled in a two-week period.
Bain
Marcus A
MA
Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
Faull
Randall
R
Milne
Robert W
RW
Evans
Allan M
AM
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002331:Carnitine / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D006435:Renal Dialysis
D008744:Methylamines; C005855:trimethyloxamine; C023336:trimethylamine; D002331:Carnitine