title: Pharmacokinetics of L-carnitine in patients with end-stage renal disease undergoing long-term hemodialysis.
abstract: OBJECTIVE
  L-Carnitine is an endogenous molecule involved in fatty acid metabolism. Secondary carnitine deficiency may develop in patients with end-stage renal disease undergoing long-term hemodialysis because of dialytic loss. In these patients L-carnitine can be administered to restore plasma and tissue levels. The objective of this study was to evaluate the pharmacokinetics of intravenous L-carnitine in patients undergoing long-term hemodialysis.
  
  
  METHODS
  Twelve patients undergoing three dialysis sessions/week received L-carnitine intravenously (20 mg x kg(-1)) at the end of each dialysis session for 9 weeks. Plasma samples were analyzed for L-carnitine, acetyl-L-carnitine, and total carnitine by HPLC.
  
  
  RESULTS
  Under baseline conditions, the mean +/- SD predialysis plasma concentration of L-carnitine was 19.5 +/- 5.6 micromol/L, decreasing to 5.6 +/- 1.9 micromol/L at the end of the dialysis session. These concentrations were substantially lower than endogenous levels in healthy human beings. Under baseline conditions the extraction ratios of L-carnitine and acetyl-L-carnitine by the dialyser were 0.74 +/- 0.07 and 0.71 +/- 0.11, respectively. During repeated dosing, there was accumulation of L-carnitine in plasma, and after 9 weeks of dosing, the predialysis and postdialysis plasma levels were 191 +/- 54.1 and 41.8 +/- 13.0 micromol/L, respectively. The predialysis and postdialysis plasma levels of L-carnitine decreased once dosing was ceased but had not returned to pretreatment levels after 6 weeks.
  
  
  CONCLUSIONS
  The study demonstrated that removal of L-carnitine by hemodialysis is extremely efficient and that patients undergoing hemodialysis had plasma concentrations that were substantially lower than normal, particularly during dialysis. During repeated administration of L-carnitine, the predialysis and postdialysis concentrations of the compound increased steadily, reaching an apparent steady state after about 8 weeks. It is proposed that this accumulation arose from the distribution of L-carnitine into a deep tissue pool that includes skeletal muscle.
authors.affiliation: Centre for Pharmaceutical Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide. allan.evans@unisa.edu.au
authors.forename: A M
authors.initials: AM
authors.lastname: Evans
authors.forename: R
authors.initials: R
authors.lastname: Faull
authors.forename: G
authors.initials: G
authors.lastname: Fornasini
authors.forename: E F
authors.initials: EF
authors.lastname: Lemanowicz
authors.forename: A
authors.initials: A
authors.lastname: Longo
authors.forename: S
authors.initials: S
authors.lastname: Pace
authors.forename: R L
authors.initials: RL
authors.lastname: Nation
mesh_terms: D000108:Acetylcarnitine / Q000097:blood; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D002331:Carnitine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000628:therapy*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis
chemical_list: D000108:Acetylcarnitine; D002331:Carnitine