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

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.