Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 May;103(1):1179–1183. doi: 10.1111/j.1476-5381.1991.tb12320.x

Short-term effects of administration of anticonvulsant drugs on free carnitine and acylcarnitine in mouse serum and tissues.

M F Camiña 1, I Rozas 1, M Gómez 1, J M Paz 1, C Alonso 1, S Rodriguez-Segade 1
PMCID: PMC1908100  PMID: 1878756

Abstract

1. The short-term evolution of concentrations of free carnitine and acylcarnitine was studied in the serum, liver, kidney, heart and skeletal muscle of mice after administration of single therapeutic doses of the anticonvulsant drugs, valproic acid (VPA), carbamazepine (CBZ), phenytoin (PHT) and phenobarbitone (PHB). 2. The effects of the drugs were immediate but transitory, control levels of free carnitine and acylcarnitine having been recovered or almost recovered in serum and in all tissues 8 h post administration (p.a.). 3. VPA was the only drug that significantly reduced free carnitine concentration in serum, which recovered control levels by 4 h p.a. 4. All the drugs studied brought about marked deficits of serum acylcarnitine, which had disappeared 2 h p.a. in the case of VPA and not until 8 h p.a. for CBZ, PHT or PHB. 5. The minimum concentrations of free carnitine and acylcarnitine in serum were invariably associated with the maximum concentration of drug in serum. 6. Free carnitine concentration was not affected by VPA in any tissue, PHT and PHB brought about significant deficits in heart and kidney, and CBZ a significant deficit in muscle. 7. Acylcarnitine concentration was significantly reduced in heart, kidney and muscle by CBZ, PHT and PHB, but in liver the effects of all drugs were very small. 8. These results are compatible with the hypothesis that the primary cause of anticonvulsant-induced alteration of carnitine metabolism is interference with renal reabsorption of carnitine.

Full text

PDF
1179

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Borum P. R., Bennett S. G. Carnitine as an essential nutrient. J Am Coll Nutr. 1986;5(2):177–182. doi: 10.1080/07315724.1986.10720124. [DOI] [PubMed] [Google Scholar]
  2. Brooks D. E., McIntosh J. E. Turnover of carnitine by rat tissues. Biochem J. 1975 Jun;148(3):439–445. doi: 10.1042/bj1480439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Böhles H., Richter K., Wagner-Thiessen E., Schäfer H. Decreased serum carnitine in valproate induced Reye syndrome. Eur J Pediatr. 1982 Nov;139(3):185–186. doi: 10.1007/BF01377353. [DOI] [PubMed] [Google Scholar]
  4. Coulter D. L. Carnitine deficiency: a possible mechanism for valproate hepatotoxicity. Lancet. 1984 Mar 24;1(8378):689–689. doi: 10.1016/s0140-6736(84)92209-8. [DOI] [PubMed] [Google Scholar]
  5. Glasgow A. M., Eng G., Engel A. G. Systemic carnitine deficiency simulating recurrent Reye syndrome. J Pediatr. 1980 May;96(5):889–891. doi: 10.1016/s0022-3476(80)80571-3. [DOI] [PubMed] [Google Scholar]
  6. Goulatia R. K., Verma A., Mishra N. K., Ahuja G. K. Disappearing CT lesions in epilepsy. Epilepsia. 1987 Sep-Oct;28(5):523–527. doi: 10.1111/j.1528-1157.1987.tb03682.x. [DOI] [PubMed] [Google Scholar]
  7. Laub M. C., Paetzke-Brunner I., Jaeger G. Serum carnitine during valproic acid therapy. Epilepsia. 1986 Sep-Oct;27(5):559–562. doi: 10.1111/j.1528-1157.1986.tb03584.x. [DOI] [PubMed] [Google Scholar]
  8. Matsuda I., Ohtani Y. Carnitine status in Reye and Reye-like syndromes. Pediatr Neurol. 1986 Mar-Apr;2(2):90–94. doi: 10.1016/0887-8994(86)90062-7. [DOI] [PubMed] [Google Scholar]
  9. Matsuda I., Ohtani Y., Ninomiya N. Renal handling of carnitine in children with carnitine deficiency and hyperammonemia associated with valproate therapy. J Pediatr. 1986 Jul;109(1):131–134. doi: 10.1016/s0022-3476(86)80592-3. [DOI] [PubMed] [Google Scholar]
  10. McGarry J. D., Foster D. W. An improved and simplified radioisotopic assay for the determination of free and esterified carnitine. J Lipid Res. 1976 May;17(3):277–281. [PubMed] [Google Scholar]
  11. Millington D. S., Bohan T. P., Roe C. R., Yergey A. L., Liberato D. J. Valproylcarnitine: a novel drug metabolite identified by fast atom bombardment and thermospray liquid chromatography-mass spectrometry. Clin Chim Acta. 1985 Jan 15;145(1):69–76. doi: 10.1016/0009-8981(85)90020-8. [DOI] [PubMed] [Google Scholar]
  12. Morita J., Yuge K., Yoshino M. Hypocarnitinemia in the handicapped individuals who receive a polypharmacy of antiepileptic drugs. Neuropediatrics. 1986 Nov;17(4):203–205. doi: 10.1055/s-2008-1052530. [DOI] [PubMed] [Google Scholar]
  13. Murphy J. V., Marquardt K. M., Shug A. L. Valproic acid associated abnormalities of carnitine metabolism. Lancet. 1985 Apr 6;1(8432):820–821. doi: 10.1016/s0140-6736(85)91481-3. [DOI] [PubMed] [Google Scholar]
  14. Nishida N., Sugimoto T., Araki A., Woo M., Sakane Y., Kobayashi Y. Carnitine metabolism in valproate-treated rats: the effect of L-carnitine supplementation. Pediatr Res. 1987 Nov;22(5):500–503. doi: 10.1203/00006450-198711000-00003. [DOI] [PubMed] [Google Scholar]
  15. Ohtani Y., Endo F., Matsuda I. Carnitine deficiency and hyperammonemia associated with valproic acid therapy. J Pediatr. 1982 Nov;101(5):782–785. doi: 10.1016/s0022-3476(82)80320-x. [DOI] [PubMed] [Google Scholar]
  16. Rodriguez-Segade S., de la Peña C. A., Paz J. M., Del Rio R. Determination of L-carnitine in serum, and implementation on the ABA-100 and CentrifiChem 600. Clin Chem. 1985 May;31(5):754–757. [PubMed] [Google Scholar]
  17. Rodriguez-Segade S., de la Peña C. A., Tutor J. C., Paz J. M., Fernandez M. P., Rozas I., Del Río R. Carnitine deficiency associated with anticonvulsant therapy. Clin Chim Acta. 1989 May 15;181(2):175–181. doi: 10.1016/0009-8981(89)90185-x. [DOI] [PubMed] [Google Scholar]
  18. Rozas I., Camiña M. F., Paz J. M., Alonso C., Castro-Gago M., Rodriguez-Segade S. Effects of acute valproate administration on carnitine metabolism in mouse serum and tissues. Biochem Pharmacol. 1990 Jan 1;39(1):181–185. doi: 10.1016/0006-2952(90)90663-6. [DOI] [PubMed] [Google Scholar]
  19. Stumpf D. A., Parker W. D., Jr, Angelini C. Carnitine deficiency, organic acidemias, and Reye's syndrome. Neurology. 1985 Jul;35(7):1041–1045. doi: 10.1212/wnl.35.7.1041. [DOI] [PubMed] [Google Scholar]
  20. Thurston J. H., Carroll J. E., Dodson W. E., Hauhart R. E., Tasch V. Chronic valproate administration reduces fasting ketonemia in children. Neurology. 1983 Oct;33(10):1348–1350. doi: 10.1212/wnl.33.10.1348. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES