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.
Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Cytochrome P-450 CYP3A/genetics , Factor Xa Inhibitors/pharmacokinetics , Pharmacogenomic Variants/genetics , Rivaroxaban/pharmacokinetics , Thrombosis/prevention & control , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Aged , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Knee/adverse effects , Cytochrome P-450 CYP3A/metabolism , Drug Monitoring/methods , Factor Xa Inhibitors/administration & dosage , Female , Haplotypes , Humans , Male , Middle Aged , Prothrombin Time , Rivaroxaban/administration & dosage , Thrombosis/etiology , Treatment OutcomeABSTRACT
The bunyaviral monogeneric family Nairoviridae currently includes 12 species for 35 distinct viruses. Here, we present the complete genome coding sequences of an additional seven nairoviruses. Five of them can be assigned to established species, whereas two of them (Artashat and Chim viruses) ought to be assigned to two novel species.
