• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of bmjcredBMJ helping doctors make better decisionsSearchLatest content
Br Med J (Clin Res Ed). Jan 30, 1982; 284(6312): 295–299.
PMCID: PMC1495859

Impaired oxidation of debrisoquine in patients with perhexiline neuropathy.

Abstract

The use of perhexiline maleate as an antianginal agent is occasionally associated with side effects, particularly neuropathy and liver damage. The reason why some individuals develop these toxic reactions is not clear, though some evidence suggests that they may result from impaired oxidative metabolism, due to genetic or hepatic factors, and consequential accumulation of the drug in toxic concentrations. Drug oxidation was measured with an oxidation phenotyping procedure in 34 patients treated with perhexiline, 20 of whom had developed neuropathy and 14 of whom had not. Most of the 20 patients with neuropathy, but not the unaffected patients, showed an impaired ability to effect metabolic drug oxidation. This impairment was independent of hepatic function, concurrent drug therapy, or tobacco or alcohol consumption. The fact that the ability to oxidise several drugs is genetically controlled points to a genetic susceptibility to developing neuropathy in response to perhexiline. Routine determination of the drug oxidation phenotype might lead to safer use of perhexiline by predicting patients who may be more at risk of developing a neuropathic reaction associated with its long-term use.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Sukerman M. Proceedings: Clinical evaluation of perhexiline maleate in the treatment of chronic cardiac arrhythmias of patients with coronary heart disease. Postgrad Med J. 1973 Apr;49(Suppl):46–52. [PubMed]
  • Gitlin N. Perhexiline maleate in the management of patients with angina pectoris. A long-term assessment. S Afr Med J. 1974 May 4;48(21):904–906. [PubMed]
  • Abaza A, Cattan D, Aziza C, Pappo E. Lettre: Effets secondaires mais réversibles á la prise de perhexiline. Nouv Presse Med. 1973 Nov 24;2(42):2820–2820. [PubMed]
  • Lewis D, Wainwright HC, Kew MC, Zwi S, Isaacson C. Liver damage associated with perhexiline maleate. Gut. 1979 Mar;20(3):186–189. [PMC free article] [PubMed]
  • Pessayre D, Bichara M, Degott C, Potet F, Benhamou JP, Feldmann G. Perhexiline maleate-induced cirrhosis. Gastroenterology. 1979 Jan;76(1):170–177. [PubMed]
  • Houdent CE, Wolf LM, Corriat A. Liver during perhexiline hypoglycaemia. Lancet. 1977 Nov 12;2(8046):1028–1028. [PubMed]
  • Tomlinson IW, Rosenthal FD. Proximal myopathy after perhexiline maleate treatment. Br Med J. 1977 May 21;1(6072):1319–1320. [PMC free article] [PubMed]
  • Hutchinson WM, Williams J, Gawler J. Papilloedema in patients taking perhexiline maleate. Br Med J. 1978 Feb 4;1(6108):305–305. [PMC free article] [PubMed]
  • Atkinson AB, McAreavey D, Trope G. Papilloedema and hepatic dysfunction apparently induced by perhexiline maleate (Pexid). Br Heart J. 1980 Apr;43(4):490–491. [PMC free article] [PubMed]
  • Lhermitte F, Fardeau M, Chedru F, Mallecourt J. Polyneuropathy after perhexiline maleate therapy. Br Med J. 1976 May 22;1(6020):1256–1256. [PMC free article] [PubMed]
  • Singlas E, Goujet MA, Simon P. Pharmacokinetics of perhexiline maleate in anginal patients with and without peripheral neuropathy. Eur J Clin Pharmacol. 1978 Nov 27;14(3):195–201. [PubMed]
  • Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL. Polymorphic hydroxylation of Debrisoquine in man. Lancet. 1977 Sep 17;2(8038):584–586. [PubMed]
  • Sloan TP, Mahgoub A, Lancaster R, Idle JR, Smith RL. Polymorphism of carbon oxidation of drugs and clinical implications. Br Med J. 1978 Sep 2;2(6138):655–657. [PMC free article] [PubMed]
  • Evans DA, Mahgoub A, Sloan TP, Idle JR, Smith RL. A family and population study of the genetic polymorphism of debrisoquine oxidation in a white British population. J Med Genet. 1980 Apr;17(2):102–105. [PMC free article] [PubMed]
  • Sloan TP, Idle JR, Smith RL. Influence of DH/DL alleles regulating debrisoquine oxidation on phenytoin hydroxylation. Clin Pharmacol Ther. 1981 Apr;29(4):493–497. [PubMed]
  • Shah RR, Oates NS, Idle JR, Smith RL. Genetic impairment of phenformin metabolism. Lancet. 1980 May 24;1(8178):1147–1147. [PubMed]
  • Ritchie JC, Sloan TP, Idle JR, Smith RL. Toxicological implications of polymorphic drug metabolism. Ciba Found Symp. 1980;76:219–244. [PubMed]
  • Williams RL, Mamelok RD. Hepatic disease and drug pharmacokinetics. Clin Pharmacokinet. 1980 Nov-Dec;5(6):528–547. [PubMed]
  • BRODIE BB, BURNS JJ, WEINER M. Metabolism of drugs in subjects with Laennec's cirrhosis. Med Exp Int J Exp Med. 1959;1:290–292. [PubMed]
  • NELSON E. RATE OF METABOLISM OF TOLBUTAMIDE IN TEST SUBJECTS WITH LIVER DISEASE OR WITH IMPAIRED RENAL FUNCTION. Am J Med Sci. 1964 Dec;248:657–659. [PubMed]
  • von Oldershausen HF, Held H, Remmer H. Kurze wissenschaftliche Mitteilungen. Klin Wochenschr. 1970 May 1;48(9):565–567. [PubMed]
  • Levi AJ, Sherlock S, Walker D. Phenylbutazone and isoniazid metabolism in patients with liver disease in relation to previous drug therapy. Lancet. 1968 Jun 15;1(7555):1275–1279. [PubMed]
  • Held H, von Oldershausen HF. Zur Pharmakokinetik von Meprobamat bei chronischen Hepatopathien und Arzneimittelsucht. Klin Wochenschr. 1969 Jan 15;47(2):78–80. [PubMed]
  • Pollet S, Hauw JJ, Escourolle R, Baumann N. Peripheral-nerve lipid abnormalities in patients on perhexiline maleate. Lancet. 1977 Jun 11;1(8024):1258–1258. [PubMed]
  • Idle JR, Mahgoub A, Lancaster R, Smith RL. Hypotensive response to debrisoquine and hydroxylation phenotype. Life Sci. 1978 Mar;22(11):979–983. [PubMed]
  • Oates NS, Shah RR, Idle JR, Smith RL. Phenformin-induced lacticacidosis associated with impaired debrisoquine hydroxylation. Lancet. 1981 Apr 11;1(8224):837–838. [PubMed]
  • Bertilsson L, Mellström B, Sjökvist F, Mårtenson B, Asberg M. Slow hydroxylation of nortriptyline and concomitant poor debrisoquine hydroxylation: clinical implications. Lancet. 1981 Mar 7;1(8219):560–561. [PubMed]

Articles from British Medical Journal (Clinical Research Ed.) are provided here courtesy of BMJ Publishing Group

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links