The population pharmacokinetics of racemic warfarin was evaluated using 613 measured warfarin plasma concentrations from 32 adult hospitalized patients and 131 adult outpatients. Warfarin concentrations were measured in duplicate using a high-performance liquid chromatographic procedure. The pharmacokinetic model used was a one-compartment open model with first-order absorption (absorption rate constant set equal to 47 day-1) and first-order elimination. The extent of availability was assumed to be one. A linear regression model was used to evaluate the influence of various demographic factors on warfarin oral clearance. Age appeared to be an important determinant of warfarin clearance in this adult population. There was about a 1%/year decrease in oral clearance over the age range of 20-70 years. Smoking appeared to result in a 10% increase in warfarin clearance, while coadministration of the inducers phenytoin or phenobarbital yielded about a 30% increase in clearance. This study has yielded a predictive model that, when combined with appropriate pharmacological response data, may be useful in the design and adjustment of warfarin regimens.
The prothrombin time (PT) is frequently performed to monitor anticoagulant therapy. Although relatively simple to perform, it requires venipuncture and laboratory resources for sample handling and analysis. A recently developed capillary whole blood device that uses fingerstick samples was evaluated. Paired capillary whole blood and reference plasma PTs were performed in 858 samples from 732 subjects. The PT for normal volunteers (n = 193) was 11.8 +/- 0.9 seconds with the use of the new instrument and 12.1 +/- 0.5 seconds with the use of the reference method. In samples from 539 patients receiving anticoagulants, the correlation coefficient between the two methods was 0.96. Venous whole blood without anticoagulant and capillary whole blood gave equivalent results, which suggests that the fingersticks do not effect the quality of the specimen. Variation in hematocrit between 23.4% (0.34) and 53.8% (0.538) did not alter the performance of the instrument. The new instrument is easy to use and may allow testing by nonlaboratory personnel and patients. It obviates the need for venipuncture, provides immediate results, and appears to be comparable in accuracy to current reference methods.
Failure to adequately anticoagulate the blood of patients receiving recombinant tissue plasminogen activator (TPA) leads to greater rates of rethrombosis. In a multicentered, randomized trial in 51 patients we compared the ability to achieve and maintain therapeutic anticoagulation by use of computer-assisted heparin therapy or the GUSTO (Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries) heparin nomogram guidelines in patients with myocardial infarction treated with recombinant TPA. Heparin therapy was initiated with either computer-generated starting doses or GUSTO guideline starting doses. Activated partial thromboplastin times were measured every 6 to 8 hours for the first 24 hours. The therapeutic range used in this trial was 1.5 to 2.5 times the patient's baseline activated partial thromboplastin time (APTT). Ninety-four percent of the APTT ratios in the computer group were equal to or greater than 1.5 in the first 24 hours compared with 78% in the GUSTO group (p < 0.009). No significant difference in bleeding was found (7.7% for GUSTO; 4.2% for computer). Incremental time-dependent changes in heparin dose were found (day 1, 1110 +/- 243 units/hr, APTT ratio = 2.5 +/- 1.4; day 3, 1380 +/- 374 units/hr, APTT ratio, 1.9 +/- 0.4). Computer-assisted heparin therapy TPA results in superior anticoagulation accuracy compared with the GUSTO guidelines. In addition, the pharmacodynamic response to heparin changes in the 2 to 3 days after administration of TPA, leading to greater heparin requirements.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.