Dmitry Sychev1, Radik Minnigulov2, Pavel Bochkov3, Kristina Ryzhikova4, Irina Yudina5, Aleksey Lychagin6, Tatyana Morozova7. 1. Clinical Pharmacology and Therapy, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation. 2. Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow, 119991, Russian Federation. radik.minnigulov@gmail.com. 3. Personalized Medicine Department, Research Center, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation. 4. Department of Molecular Biological Research, Research Center, Russian Medical Academy of Continuous Professional Education, 2/1 Barrikadnaya St., Moscow, 123242, Russian Federation. 5. Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow, 119991, Russian Federation. 6. Department of Traumatology, Orthopedics and Disaster Surgery, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow, 119991, Russian Federation. 7. Department of General Medical Practice, I.M. Sechenov First Moscow State Medical University (Sechenov University), 8-2 Trubetskaya St., Moscow, 119991, Russian Federation.
Abstract
INTRODUCTION: Population ageing in developed countries will inevitably increase the need for knee and hip replacement surgery. Over the years, direct oral anticoagulants, such as rivaroxaban, have been widely used for thromboprophylaxis in patients undergoing knee and hip replacement surgery. The study of pharmacogenetic characteristics of rivaroxaban is important for enhancing the effectiveness and safety of rivaroxaban thromboprophylaxis. AIM: Evaluation of CYP3A4, CYP3A5 and ABCB1 gene polymorphisms influence on rivaroxaban pharmacokinetics and prothrombin time dynamics in patients undergoing total hip and knee replacement surgery. METHODS: The study included 78 patients undergoing total hip and knee replacement surgery. The patients received 10 mg of rivaroxaban once a day. Genotyping of polymorphisms ABCB1 rs1045642, ABCB1 rs4148738, CYP3A4 rs35599367 and CYP3A5 rs776746 was performed. Peak steady-state and trough steady-state rivaroxaban concentrations were determined. Prothrombin time was also evaluated. RESULTS: The study revealed the following haplotypes: (1) ABCB1 rs1045642-CYP3A4 rs35599367 and (2) ABCB1 rs4148738-CYP3A4 rs35599367. The analysis of the peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes revealed no significant differences. However, there was a statistically significant average correlation between peak steady-state rivaroxaban concentration and prothrombin time (r = 0.421; r2 = 0.178; p < 0.001). CONCLUSION: No significant difference was identified in peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes. The revealed statistically significant average correlation between the prothrombin time and peak steady-state rivaroxaban concentration is important in clinical practice for assessing the anticoagulant activity of rivaroxaban.
INTRODUCTION: Population ageing in developed countries will inevitably increase the need for knee and hip replacement surgery. Over the years, direct oral anticoagulants, such as rivaroxaban, have been widely used for thromboprophylaxis in patients undergoing knee and hip replacement surgery. The study of pharmacogenetic characteristics of rivaroxaban is important for enhancing the effectiveness and safety of rivaroxaban thromboprophylaxis. AIM: Evaluation of CYP3A4, CYP3A5 and ABCB1 gene polymorphisms influence on rivaroxaban pharmacokinetics and prothrombin time dynamics in patients undergoing total hip and knee replacement surgery. METHODS: The study included 78 patients undergoing total hip and knee replacement surgery. The patients received 10 mg of rivaroxaban once a day. Genotyping of polymorphisms ABCB1rs1045642, ABCB1rs4148738, CYP3A4rs35599367 and CYP3A5rs776746 was performed. Peak steady-state and trough steady-state rivaroxaban concentrations were determined. Prothrombin time was also evaluated. RESULTS: The study revealed the following haplotypes: (1) ABCB1rs1045642-CYP3A4rs35599367 and (2) ABCB1rs4148738-CYP3A4rs35599367. The analysis of the peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes revealed no significant differences. However, there was a statistically significant average correlation between peak steady-state rivaroxaban concentration and prothrombin time (r = 0.421; r2 = 0.178; p < 0.001). CONCLUSION: No significant difference was identified in peak steady-state rivaroxaban concentration between mutant haplotypes and wild haplotypes. The revealed statistically significant average correlation between the prothrombin time and peak steady-state rivaroxaban concentration is important in clinical practice for assessing the anticoagulant activity of rivaroxaban.
Entities:
Keywords:
Drug concentration; Gene polymorphisms; P-glycoprotein; Pharmacogenetics; Rivaroxaban; Thromboprophylaxis
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