BACKGROUND Warfarin is an anticoagulant with a narrow therapeutic index that is involved in a number of drug-drug interactions. OBJECTIVES This study evaluates the potential effect of odanacatib (a cathepsin K inhibitor in development for the treatment of osteoporosis) on the pharmacokinetics and pharmacodynamics of warfarin. METHODS In a randomized, open-label, two-period fixed-sequence de...

BACKGROUND People infected with HIV are prone to venous thrombosis. Treatment of thrombosis is primarily with warfarin. No studies have addressed the effects of HIV infection on warfarin dose. The aims of this study were to determine whether the therapeutic dose of warfarin and induction time to therapeutic dose in HIV-infected patients differ from that in HIV-uninfected patients. METHODS A p...

OBJECTIVE To determine whether warfarin can be safely administered to children who require long-term total parenteral nutrition (TPN), for the purpose of preventing central venous access device (CVAD)-related thrombosis. METHODS A prospective cohort study was conducted of 8 children with short-gut syndrome or small intestinal anomalies. All patients received oral anticoagulant therapy (warfar...

OBJECTIVE Variants of two genes, CYP2C9 and VKORC1, explain approximately one third of variability in warfarin maintenance dose requirements. However, the clinical utility of using this information in addition to clinical and demographic data ('pharmacogenomic-guidance') is unclear, as few comparative clinical trials have been conducted to date. The objective of this study was to explore the in...

OBJECTIVE To determine the warfarin maintenance dose in Iranian patients. METHODS This multicenter study was conducted between January 2007 and January 2008 in 5 different large cities of Iran. Patients older than 12 years receiving warfarin were included. During the first days of warfarin use, international normalized ration (INR) was measured daily and after that every 1-2 weeks, with a dur...

Objective: Validation of analysis method is important, especially in analyzing narrow-index drugs such as warfarin (WF). This study aimed to obtain a validated human plasma according European Medicine Agency guidelines.
 Methods: The optimum conditions for the using fluorescence detector HPLC with Chiralcel OD-RH column (4.6 x 150 mm i.d., 5μm); guard (4.0 10 mm, 5μm), temperature 45 °C. m...

Genetic polymorphisms in the gene encoding cytochrome P450 (CYP) 4F2, a vitamin K oxidase, affect stable warfarin dose requirements and time to therapeutic INR. CYP4F2 is part of the CYP4F gene cluster, which is highly polymorphic and exhibits a high degree of linkage disequilibrium, making it difficult to define causal variants. Our objective was to examine the effect of genetic variability in...

OBJECTIVE To study the performance of pharmacogenetics-based warfarin dosing algorithms in the initial and the stable warfarin treatment phases in a cohort of Han-Chinese patients undertaking mechanic heart valve replacement. METHODS We searched PubMed, Chinese National Knowledge Infrastructure and Wanfang databases for selecting pharmacogenetics-based warfarin dosing models. Patients with me...

PURPOSE The genes for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) have been identified as important genetic determinants of warfarin dosing and have been studied. We developed warfarin algorithm for Korean patients with stroke and compared the accuracy of warfarin dose prediction algorithms based on the pharmacogenetics. MATERIALS AND METHODS A tota...

This case describes the increased anticoagulation effect associated with the use of high-dose ketoconazole. A 59-year-old man treated with warfarin for aortic valve replacement was prescribed high-dose ketoconazole and hydrocortisone for the treatment of prostate cancer. Despite lowering the warfarin dosage by 35% during the start of high dose ketoconazole, an additional dose reduction was requ...