PHARMACOKINETIC OPTIMIZATION OF THE TREATMENT OF DEEP-VEIN THROMBOSIS

The current treatment for deep vein thrombosis is a 5- to 10-day cours e of heparin followed by 3 to 6 months of oral anticoagulants. Both he parin and oral anticoagulants present a high inter- and intra-individu al variability and require individualisation and monitoring of their d osage. The pharmacokinetic properties of heparin have been difficult t o assess through the radiolabelling procedures typically used for many other drugs, This is partially a result of the heterogeneous nature o f heparin. Thus, the pharmacokinetics of heparin are expressed in term s of its pharmacodynamic activity, Improved coagulation test methodolo gy coupled with the incorporation of patient factors such as bodyweigh t, height, baseline coagulation status, pretreatment heparin sensitivi ty and heparin concentrations, can be used to improve the accuracy of heparin dosage determination, Computer-based systems are now available to assist clinicians in quantitating dosage requirements, estimating bleeding risks, and storing patient dose-response relationships for fu ture therapy monitoring. Low molecular weight heparin products might i mprove our ability to control anticoagulant therapy because drug conce ntration, as well as the effect on the clotting system, will be more p redictable in patients receiving these products, In addition, low mole cular weight heparins produce a more consistent, predictable anticoagu lant response, and clinicians have a new pharmacological tool which ma y readily lend itself to patient-controlled, home-based anticoagulant pharmacotherapy. Where pharmacokinetics and pharmacodynamics could con tribute to the optimisation of warfarin treatment is in the initiation of treatment, the estimation of the dosage required, the methods for drug monitoring, the assessment of unusual responses and the avoidance of drug interactions. Traditional pharmacokinetic methods have limite d applicability to the optimisation of warfarin therapy because there is no direct relationship between drug concentration and therapeutic e ffect. However, a variety of simple or sophisticated computer-assisted methods have been developed to help clinicians in individualising and monitoring warfarin treatment. New therapeutic approaches, such as di rect thrombin inhibitors and thrombolytic agents, could overcome some limitations of the standard heparin plus oral anticoagulation therapy.