PMID: 8946814Nov 1, 1996Paper

Cyclophosphamide-induced acute liver failure requiring transplantation in a patient with genetically deficient debrisoquine metabolism: a causal relationship?

Journal of Internal Medicine
L L GustafssonA Nyberg

Abstract

Severe liver damage can occur after treatment with cyclophosphamide. The possible linkage to genetically deficient drug metabolic capacity is unknown. A 58-year-old woman with rheumatoid arthritis was treated with oral cyclophosphamide 50 mg twice daily for 2 months. Due to poor response the dose was doubled and liver failure requiring transplantation developed within weeks. After surgery PCR amplification using DNA from leukocytes showed that she was homozygous for the mutated allele CYP2D6B, which is predictive of the poor metaboliser phenotype for debrisoquine, occurring in 7% of Caucasians. Our patient may have accumulated high levels of the hepatotoxic 4-hydroxylated cyclophosphamide metabolite. Pharmacogenetic methods can help in exploring mechanisms of unexpected severe adverse effects.

Citations

Jan 18, 2006·Digestive Diseases and Sciences·Luigi MuratoriFrancesco B Bianchi
Oct 15, 2009·Biological Trace Element Research·Adnan AyhanciSuzan Yaman
Feb 11, 1999·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·I A al-Nasser
Jan 20, 2016·Canadian Journal of Physiology and Pharmacology·Eman SaidRania R Abdelaziz
Jun 6, 2006·Clinica Chimica Acta; International Journal of Clinical Chemistry·Emila SugumarPremila Abraham
Jul 14, 2010·Human & Experimental Toxicology·Premila Abraham, Bina Isaac
Jun 7, 2006·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Lydia TchambazStephan Krähenbühl
Mar 10, 2000·The American Journal of Gastroenterology·C C MokC L Lai
Nov 1, 2018·Rheumatology International·Döndü Üsküdar CansuCengiz Korkmaz
Nov 23, 2007·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Premila Abraham, Emila Sugumar

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