The case of dynamic intestinal obstruction, caused by an individual intolerance to vincristine in a child of 5 years
https://doi.org/10.30895/2312-7821-2018-6-1-32-35
Abstract
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.
About the Authors
S. S Postnikov
Russian National Research Medical University named after N.I. Pirogov; Russian Children’s Clinical Hospital.
Russian Federation
Postnikov Sergey S. Professor of the Department of Clinical Pharmacology, MD, DSc (Med); Clinical pharmacologist, MD, DSc (Med).
Russian Federation
Postnikov Sergey S. Professor of the Department of Clinical Pharmacology, MD, DSc (Med); Clinical pharmacologist, MD, DSc (Med).
V. A. Strykov
Russian Children’s Clinical Hospital.
Russian Federation
Strykov Vladimir A. Head of the Department of Oncology, PhD.
Russian Federation
Strykov Vladimir A. Head of the Department of Oncology, PhD.
M. N. Kostyleva
Russian National Research Medical University named after N.I. Pirogov; Russian Children’s Clinical Hospital.
Russian Federation
Kostyleva Maria N. Associate Professor of the Department of Clinical Pharmacology, PhD.
Russian Federation
Kostyleva Maria N. Associate Professor of the Department of Clinical Pharmacology, PhD.
E. S. Ilina
Russian Children’s Clinical Hospital.
Russian Federation
Ilina Elena S. Head of the Department of Psychoneurology No. 2, PhD.
Russian Federation
Ilina Elena S. Head of the Department of Psychoneurology No. 2, PhD.
A. N. Gracianskaya
Russian National Research Medical University named after N.I. Pirogov.
Russian Federation
Russian Federation
Gracianskaya Anna N. Associate Professor of the Department of Clinical Pharmacology, PhD.
A. B. Strock
Russian Children’s Clinical Hospital.
Russian Federation
Russian Federation
Strock Alina B. Clinical pharmacologist, PhD
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Review
For citations:
Postnikov S.S., Strykov V.A., Kostyleva M.N., Ilina E.S., Gracianskaya A.N., Strock A.B. The case of dynamic intestinal obstruction, caused by an individual intolerance to vincristine in a child of 5 years. Safety and Risk of Pharmacotherapy. 2018;6(1):32-35. (In Russ.) https://doi.org/10.30895/2312-7821-2018-6-1-32-35
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