Uptake of L-carnitine and its short-chain ester propionyl-L-carnitine in the isolated perfused rat liver

Journal of Pharmacology and Experimental Therapeutics

Volumn 315, Issue 1, 2005, Pages 118-124

  Mancinelli, Angelo ^a   Evans, Allan M ^b   Nation, Roger L ^c   Longo, Antonio ^a  

^a Sigma Tau SpA   (Italy)

^b UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

^c MONASH UNIVERSITY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CARNITINE; PROPIONYLCARNITINE; SUCROSE;

ANIMAL EXPERIMENT; ARTICLE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DRUG UPTAKE; FLOW RATE; ISOLATED LIVER; ISOTOPE LABELING; LIVER CELL; LIVER CLEARANCE; LIVER PERFUSION; MALE; MEMBRANE PERMEABILITY; MEMBRANE TRANSPORT; NONHUMAN; PORTAL VEIN; PRIORITY JOURNAL; RADIOCHEMISTRY; RAT; TRANSPORT KINETICS;

ANIMALS; BILE; CARNITINE; LIVER; MALE; PERFUSION; RATS; RATS, SPRAGUE-DAWLEY; REPRODUCIBILITY OF RESULTS;

EID: 25644443960     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.105.087890     Document Type: Article

References (40)

1. Bahl JJ and Bressler R (1987) The pharmacology of carnitine. Ann Rev Pharmacol Toxicol 27:257-277.
2. Bartels GL, Remme WJ, Pillay M, Schonfeld DH, and Cox PH (1992) Acute improvement of cardiac function with intravenous L-propionylcarnitine in humans. J Cardiovasc Pharmacol 20:157-164.
3. Böhmer T and Bremer J (1968) Propionylcarnitine: physiological variations in vivo. Biochim Biophys Acta 152:559-567.
4. Bremer J (1983) Carnitine-metabolism and functions. Physiol Rev 63:1420-1480.
5. Brevetti G, Perna S, Sabbà C, Rossini A, Scotto DI, Uccio V, Berardi E, and Godi L (1992) Superiority of L-propionyl-carnitine vs L-carnitine in improving walking capacity in patients with peripheral vascular disease. An acute, intravenous, double-blind, crossover study. Eur Heart J 13:251-255.
6. Chou CH, Evans AM, Fornasini G, and Rowland M (1993) Relationship between lipophilicity and hepatic dispersion and distribution for a homologous series of barbiturates in the isolated perfused in situ rat liver. Drug Metab Dispos 21:933-938.
7. Choudhuri S, Cherrington NJ, Li N, and Klaassen CD (2003) Constitutive expression of various xenobiotic and endobiotic transporter mRNA in the choroid plexus of rats. Drug Metab Dispos 31:1337-1345.
8. Christiansen RZ and Bremer J (1976) Active transport of butyrobetaine and carnitine into isolated liver cells. Biochim Biophys Acta 448:562-577.
9. Davenport RJ, Law MP, Pike VW, Osman S, and Poole KG (1995) Propionyl-L-carnitine: labelling in the methyl position with carbon-11 and pharmacokinetics studies in rats. Nucl Med Biol 22:699-709.
10. Duprez DA, De Buyzere ML, and Hirsch A (2003) Developing pharmaceutical treatments for peripheral artery disease. Expert Opin Investig Drugs 12:101-108.
11. Evans AM and Fornasini G (2003) Pharmacokinetics of L-carnitine. Clin Pharmacokinet 42:941-967.
12. Evans AM, Hussein Z, and Rowland M (1993) Influence of albumin on the dispersion and elimination kinetics of diclofenac in the isolated perfused rat liver: analysis by the impulse-response technique and the dispersion model. J Pharm Sci 82:421-428.
13. Evans AM, Mancinelli A, and Longo A (1997) Excretion and metabolism of propionyl-L-carnitine in the isolated perfused rat kidney. J Pharmacol Exp Ther 281:1071-1076.
14. Evans AM and Shanahan K (1995) The disposition of morphine and its metabolites in the in-situ rat isolated perfused liver. J Pharm Pharmacol 47:333-339.
15. Goa KL and Brogden RN (1987) L-Carnitine. A preliminary review of its pharmacokinetics and its therapeutic use in ischaemic heart disease and primary and secondary carnitine deficiencies in relationship to its role in fatty acid metabolism (Review). Drugs 34:1-24.
16. Goresky CA and Nadeau BE (1974) Uptake of materials by the intact liver. The exchange of glucose across the cell membranes. J Clin Investig 53:634-646.
17. Goresky CA, Schwab AJ, and Pang KS (1993) Kinetic model of hepatic transport at the organ level, in Hepatic Transport and Bile Secretion. Physiology and Pathophysiology (Tavoloni N and Berk PD eds) pp 11-39, Raven Press, New York.
18. Harper C, Elwin E, and Cederblad G (1988) Pharmacokinetics of bolus intravenous and oral doses of L-carnitine in healthy subjects. Eur J Clin Pharmacol 35:69-75.
19. Hoppel CL and Davis AT (1986) Inter-tissue relationships in the synthesis and distribution of carnitine. Biochem Soc Trans 14:673-674.
20. Ishigami M, Tokui T, Komai T, Tsukahara K, Yamazaki M, and Sugiyama Y (1995) Evaluation of the uptake of pravastatin by perfused rat liver and primary cultured rat hepatocytes. Pharm Res (NY) 12:1741-1745.
21. Lahjouji K, Mitchell GA, and Qureshi I (2001) Carnitine transport by organic cation transporters and systemic carnitine deficiency. Mol Genet Metab 73:287-297.
22. Longo A, Bruno G, Curti S, Mancinelli A, and Miotto G (1996) Determination of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine in human plasma by high-performance liquid chromatography after pre-column derivatization with l-aminoanthracene. J Chromatogr 686:129-139.
23. Kakutani T, Yamaoka K, Hashida M, and Sezaki H (1985) A new method for assessment of drug disposition in muscle: application of statistical moment theory to local perfusion systems. J Pharmacokinet Biopharm 13:609-631.
24. Koepsell H (2004) Polyspecific organic cation transporters: their functions and interactions with drugs. Trends Pharmacol Sci 25:375-381.
25. Mancinelli A, Longo A, Nation RL, and Evans AM (2000) Disposition of L-carnitine and its short-chain esters, acetyl-L-carnitine and propionyl-L-carnitine, in the rat isolated perfused liver. Drug Metab Dispos 28:1401-1404.
26. Mancinelli A, Longo A, Shanahan K, and Evans AM (1995) Disposition of L-carnitine and acetyl-L-carnitine in the isolated perfused rat kidney. J Pharmacol Exp Ther 274:1122-1128.
27. Marzo A, Arrigoni Martelli E, Mancinelli A, Cardace G, Corbelletta C, Bassani E, and Solbiati M (1991) Protein binding of L-carnitine family components. Participants Papers (Special Issue No III). Eur J Drug Metab Pharmacokinet 364-368.
28. Nakajima H, Inoue F, Kizaki Z, Terada N, Okochi M, Kinugasa A, and Sawada T (1999) Carnitine import to isolated hepatocytes and synthesis are accelerated in pivalate-treated rats. J Nutr 129:1688-1691.
29. Nezu J, Tamai I, Oku A, Ohashi R, Yabuuchi H, Hashimoto N, Nikaido H, Sai Y, Koizumi A, Shoji Y, et al. (1999) Primary systemic carnitine deficiency is caused by mutation in a gene encoding sodium ion-dependent carnitine transporter. Nat Genet 21:91-94.
30. Pessotto P, Liberati R, Petrella O, and Hulsmann WC (1996) Quaternary nitrogen compounds affect carnitine distribution in rats. Particular emphasis on edrophonium. Biochim Biophys Acta 1299:245-251.
31. Pons R and DiMauro S (1998) Primary and acquired L-carnitine deficiency. Cardiologia 43 (Suppl 2):2S671-2S676.
32. Rebouche CJ and Seim H (1998) Carnitine metabolism and its regulation in microorganisms and mammals. Annu Rev Nutr 18:39-61.
33. Sahajwalla CG, Helton ED, Purich ED, Hoppel CL, and Cabana BE (1995) Multiple-dose pharmacokinetics and bioequivalence of L-carnitine 330-mg tablet versus 1-g chewable tablet versus enteral solution in healthy adult male volunteers. J Pharm Sci 84:627-633.
34. Slitt AL, Cherrington NJ, Hartley DP, Leazer TM, and Klaassen CD (2002) Tissue distribution and renal developmental changes in rat organic cation transporter mRNA levels. Drug Metab Dispos 30:212-219.
35. Tamai I, Ohashi R, Nezu J, Yabuuchi H, Oku A, Shimane M, Sai Y, and Tsuji A (1998) Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 273:20378-20382.
36. Tamai I, Ohashi R, Nezu JI, Sai Y, Kobayashi D, Oku A, Shimane M, and Tsuji A (2000) Molecular and functional characterization of organic cation/carnitine transporter family in mice. J Biol Chem 275:40064-40072.
37. Tamai I, Yabuuchi H, Nezu J, Sai Y, Oku A, Shimane M, and Tsuji A (1997) Cloning and characterization of a novel human pH-dependent organic cation transporter, OCTN1. FEBS Lett 419:107-111.
38. Wolkoff AW, Johansen KL, and Goeser T (1987) The isolated perfused rat liver: preparation and application. Anal Biochem 167:1-14.
39. Wu X, Huang W, Prasad PD, Seth P, Rajan DV, Leibach FH, Chen J, Conway SJ, and Ganapathy V (1999) Functional characteristics and tissue distribution pattern of organic cation transporter 2 (OTN2), an organic cation/carnitine transporter. J Pharmacol Exp Ther 290:1482-1492.
40. Yokogawa K, Yonekawa M, Tamai I, Ohashi R, Tatsumi Y, Higashi Y, Nomura M, Hashimoto N, Nikaido H, Hayakawa JI, et al. (1999) Loss of wild-type carrier-mediated L-carnitine transport activity in hepatocytes of juvenile visceral steatosis mice. Hepatology 30:997-1001.