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Gilbert’s syndrome, drugs, metabolism, pharmacogenetics

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Khaitovych , M., & Turchak , D. (2020). JILBER’S SYNDROME: CLINICAL AND PHARMACOLOGICAL ASPECTS. Review. Medical Science of Ukraine (MSU), 16(4), 58-64. https://doi.org/10.32345/2664-4738.4.2020.9


Relevance. At present, the metabolism of drugs in patients with Gilbert's syndrome will be actively studied, as it may be associated with both the risk of dose-dependent adverse reactions and treatment ineffectiveness.

Objective: to summarize the information of various authors on the peculiarities of the use of drugs in patients with Gilbert's syndrome.

Methods. Analysis of scientific publications in the international electronic scientometric database PubMed by keywords. Search depth - 10 years (2010-2019).

Results. Gilbert’s syndrome is observed in 3-10% of the population and is characterized by an isolated increase of bilirubin in the blood to moderate values without changes in other biochemical parameters of liver function and without damage to its structure. Gilbert's syndrome is inherited autosomal recessively and is mainly due to the presence of an additional dinucleotide thymine-adenine (TA) in the promoter region A(TA)6TAA gene encoding the enzyme UGT1A1. Elongation of the promoter sequence reduces the formation of UGT1A1. Invariant A(TA)7TAA, the level of enzyme production can be reduced to 80% of the norm in hetero- and up to 20% in homozygotes, respectively. Gilbert’s syndrome is manifested by increased levels of indirect bilirubin in the blood, jaundice of the skin and mucous, abdominal pain, as well as dyspepsia, and asthenovegetative syndrome. Intermittent icteric sclera and skin occur against the background of exogenous and endogenous factors such as starvation, dehydration, infectious diseases, emotional and physical stress, hemolysis, menstruation, alcohol consumption, hormonal contraception, etc., usually at a bilirubin concentration exceeding 40-45 μmol/l. Complications of hyperbilirubinemia with Gilbert’s syndrome include the development of gallstone disease, including in children and adolescents. Gilbert’s syndrome is associated with impaired metabolism of some drugs – aglucones. These include anabolic steroids, glucocorticoids, androgens, rifampicin, cimetidine, chloramphenicol, streptomycin, sodium salicylate, ampicillin, caffeine, Ethinyl estradiol, paracetamol, ibuprofen, The clinical feature of Gilbert’s syndrome is the appearance or aggravation of jaundice associated with the use of such drugs. In conditions of UGT1 deficiency, drugs compete with bilirubin for the enzyme, which leads to an increase of indirect bilirubin in the serum. Therefore, to prevent liver damage, it is necessary to assess the risk and benefit of drug treatment of patients with Gilbert’s syndrome in each case.

Conclusions. Gilbert’s syndrome is a common pathological condition and therefore it is important to diagnose it as early as possible. Given that the use of aglucones in patients with Gilbert's syndrome may cause the development of drug-induced liver damage, it is necessary to assess the risk and benefit of drug treatment of patients with Gilbert’s syndrome in each case.

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