menaquinone-6 and Thromboembolism

In this decade, the field of pharmacogenomics (PGx), which is related to pharmacokinetics (PK) or pharmacodynamics (PD), has attracted much attention because it may provide a possible explanation for individual differences in the clinical efficacy of drugs. For the development of personalized drug therapy, it is important to accumulate evidence from PK/PD/PGx analysis in clinical trials. Warfarin (WF) is one of the most widely prescribed anticoagulants for the prevention and treatment of venous and arterial thromboembolism. However, large interindividual and interethnic differences have been observed in the WF dose required to elicit the anticoagulant effect. We investigated the factors influencing the WF maintenance dose in Japanese patients. Our study confirmed a large interindividual variability in the WF maintenance dose that was due to a VKORC1 1639 G>A polymorphism and differences in body weight, age, and serum albumin. In addition, we found that the CYP4F2 genotype affects the plasma concentration of menaquinone-4, and that this finding was correlated with the WF sensitivity index in Japanese pediatric patients. Methotrexate (MTX) is an antifolate that is widely used to treat rheumatoid arthritis (RA) and cancer. The response to low-dose MTX demonstrated wide interpatient variability; however, the contributing factors remain unclear. We found that the frequency of the RFC1 80A allele was higher in RA patients treated with MTX alone compared with patients who received biological disease-modifying antirheumatic drugs (bDMARDs). This finding may support the combined use of bDMARDs and MTX. Further large-scale prospective clinical trials are required to confirm these findings.

Topics: Anticoagulants; Antirheumatic Agents; Arthritis, Rheumatoid; Asian People; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 4; Drug Therapy, Combination; Gene Frequency; Humans; Maintenance Chemotherapy; Methotrexate; Pharmacokinetics; Polymorphism, Genetic; Precision Medicine; Replication Protein C; Thromboembolism; Vitamin K 2; Vitamin K Epoxide Reductases; Warfarin

Numerous algorithms based on patient genetic variants have been established with the aim of reducing the risk of GI bleeding and thromboembolism during warfarin administration. However, approximately 35 % of individual warfarin sensitivity still remains unexplained. Few of warfarin algorithms take into account gut microbiota profiles. The identification of certain microbiome will provide new targets and new strategies for reducing the risk of bleeding and thromboembolism during warfarin administration. In this study, we collected plasma and stool samples from 200 inpatients undergoing heart valve replacement (HVR), which were classified as low responder (LR), high responder (HR) and normal responder (NR). Significant differences were observed in the diversity and relative abundance of the gut microbiota among the three groups. The genus Escherichia-Shigella was enriched significantly in the LRs (P = 3.189e

Topics: Adult; Aged; Anticoagulants; Blood Coagulation; Enterococcus; Feces; Female; Gastrointestinal Microbiome; Heart Valve Prosthesis Implantation; Hemorrhage; High-Throughput Nucleotide Sequencing; Host-Pathogen Interactions; Humans; Intestines; Male; Metagenomics; Middle Aged; Ribotyping; Shiga-Toxigenic Escherichia coli; Thromboembolism; Treatment Outcome; Vitamin K 2; Warfarin