![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
A Mancinelli, A Longo, K Shanahan and AM Evans
Sigma Tau SpA, Pomezia, Rome, Italy.
The isolated perfused rat kidney was used to investigate the regulation, specificity and concentration-dependence of the renal tubular disposition of L-carnitine (LC) and its ester, acetyl-L- carnitine (ALC). Tritiated markers were used to study the renal disposition of LC and ALC and HPLC was used to purify 3H-LC and 3H-ALC before radiochemical analysis. At perfusate concentrations comparable to those found in plasma in vivo (50 microM for LC and 5 microM for ALC), the renal clearance of both analogues was substantially less than GFR (P < .05) which, in view of their negligible binding to perfusate proteins, is indicative of extensive reabsorption. During the first 20 min of perfusion, the percent tubular reabsorption (%TR) of LC and ALC was 94 +/- (SD) 2.6% and 97 +/- 0.6%, respectively. The extent of 3H- ALC and 3H-LC enrichment of perfusate in experiments with 3H-LC and 3H- ALC, respectively, provided evidence for the capability of the rat kidney to acetylate LC and deacetylate ALC. In addition, a portion of renally generated 3H-ALC and 3H-LC was found to undergo leakage into renal tubules and escape subsequent reabsorption. It was also found that the %TR of both compounds decreased substantially when the perfusate concentration was increased above endogenous levels; each compound was capable of decreasing the %TR of the other; and trimethylamine-N-oxide, a metabolite of LC, had no significant effect on the renal handling of the carnitine derivatives.
This article has been cited by other articles:
|
|
 |
|
  M. A. Bain, R. W. Milne, and A. M. Evans Disposition and Metabolite Kinetics of Oral L-carnitine in Humans. J. Clin. Pharmacol., October 1, 2006; 46(10): 1163 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Mancinelli, A. M. Evans, R. L. Nation, and A. Longo Uptake of L-Carnitine and Its Short-Chain Ester Propionyl-L-carnitine in the Isolated Perfused Rat Liver J. Pharmacol. Exp. Ther., October 1, 2005; 315(1): 118 - 124. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kuwajima, H. Harashima, M. Hayashi, S. Ise, M. Sei, K.-m. Lu, H. Kiwada, Y. Sugiyama, and K. Shima Pharmacokinetic Analysis of the Cardioprotective Effect of 3-(2,2,2-Trimethylhydrazinium) Propionate in Mice: Inhibition of Carnitine Transport in Kidney J. Pharmacol. Exp. Ther., April 1, 1999; 289(1): 93 - 102. [Abstract] [Full Text]
|
|
|
|
|
|
K. M. Shanahan, A. M. Evans, and R. L. Nation Disposition of Morphine in the Rat Isolated Perfused Kidney: Concentration Ranging Studies J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1518 - 1525. [Abstract] [Full Text]
|
|
|
|
|
|
A. M. Evans, A. Mancinelli, and A. Longo J. Pharmacol. Exp. Ther., June 1, 1997; 281(3): 1071 - 1076. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
