Personalized Approach to the Use of Macrolides in the Treatment of Complicated Forms of Acute Bacterial Rhinosinusitis

Abstract

The purpose was to assess the possibilities of applying a personalized approach to the appointment of macrolides in acute bacterial rhinosinusitis, depending on the carrier of single-nucleotide polymorphism genes. Materials and methods. An analysis of Russian and English-language publications was conducted with a search depth of 30 years. Results. The main enzymes involved in macrolide pharmacokinetics are P-gp, OATP1B1, OATP1B3, CYP3A4, MRP2. P-gp activity is higher in carriers of the homozygous genotype in the major allele C (3435CC, 48.33%) and the heterozygous genotype (3435CT, 45.90%) of the SNPs rs1045642, whereas the lowest activity was detected in the carriers of the homozygote genotype in the minor allele T (3435 TT, 31.62%), P = 0.02. SNPS 521 T> C (rs4149056) in the SLCO1B1 gene, encoding because of the need for OATP1B1*5, associated with changes in the activity of the protein that carries and erythromycin metabolizing, respectively, in homozygous carriers of the major T allele (P = 0.0072). The activity of the 3A4 isoenzyme in the liver in homozygous carriers of negative T (CC) alleles was 1.7 and 2.5 times higher than in heterozygous (ST) and homozygous (TT) carriers of the minor T allele (rs35599367). The homozygous carriage of the G major allele (rs717620) is associated with a reduced protein function, the homozygous carriage of the minor A allele is associated with an increase in the activity of the MRP2 protein. Conclusion. Genetically determined differences in the pharmacokinetics and pharmacodynamics of macrolides were detected depending on the gene carrier of the SNP ABCB1, SLCO1B1, CYP3A4, АВСС2. Knowledge of the genetically determined metabolism of macrolides in humans can provide new insights into the systemic effects that are available and clinically interesting from their appointment.