The case of dynamic intestinal obstruction, caused by an individual intolerance to vincristine in a child of 5 years

• Main Authors: S. S Postnikov, V. A. Strykov, M. N. Kostyleva, E. S. Ilina, A. N. Gracianskaya, A. B. Strock
• Format: Article
• Language: Russian
• Published: Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation 2018-03-01
• Series: Безопасность и риск фармакотерапии
• Subjects: neuroblastom; opsoklonus-myoclonus; vincristine; cytochrome p450 3a5; dynamic obstruction; undesirable side reaction
• Online Access: https://www.risksafety.ru/jour/article/view/97
• ISSN: 2312-7821; 2619-1164

One of the key enzymes involved in the first phase of biotransformation of drugs is cytochrome P450 (CYP450), represented predominantly in the liver. Vincristine is metabolized mainly by CYP3A5 (75 %) and to a lesser extent CYP3A4 (whose level is lower in children). Low expression (CYP3A5*3 genotype) or even absence of CYP3A5 (in 80 % of Caucasians) and an age-related decrease in CYP3A4 activity leads to a five-fold decrease in vincristine clearance, its cumulation and development of an undesirable side reaction (CPD) — most often peripheral neuropathy, but its characteristic feature is the reduction of achilles reflexes and distal paresis after 2–3 injections. The article presents a case of a rare side effect of vincristine — damage to the nervous apparatus of the intestine with the development of dynamic obstruction. The complication of vincristine therapy is explained by the ethno-dependent decrease / absence of cytochrome P450 3A5, which metabolizes vincristine, which leads to cumulation of the drug.