Безопасность и риск фармакотерапии (Mar 2018)

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

  • S. S Postnikov,
  • V. A. Strykov,
  • M. N. Kostyleva,
  • E. S. Ilina,
  • A. N. Gracianskaya,
  • A. B. Strock

DOI
https://doi.org/10.30895/2312-7821-2018-6-1-32-35
Journal volume & issue
Vol. 6, no. 1
pp. 32 – 35

Abstract

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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.

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