Assessment of the Potential Pharmacokinetic and Pharmacodynamic Interactions between Erythromycin and Argatroban

Tran, Jonathan Q.; Cicco, Robert A. Di; Sheth, Sunita; Tucci, Marcella G.; Peng, Lana; Jorkasky, Diane K.; Hursting, Marcie J.; Benincosa, Lisa J.

doi:10.1177/009127009903900512

Cited by 47 publications

References 19 publications

(20 reference statements)

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Anticoagulants, Antithrombotics, and Hemostatics

Bisacchi

2003

Burger's Medicinal Chemistry and Drug Discovery

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Maintenance of proper blood flow is a complex and highly regulated physiological process, with multiple complementary and opposing mechanisms of control. Imbalances in these mechanisms can lead to a variety of pathological consequences, such as hemorrhage or obstructive clot (thrombus) formation in veins or arteries, leading to stroke, pulmonary embolism, heart attack, and other serious conditions. One of the overriding challenges with current or future drug strategies for antithrombotic, thrombolytic (clot dissolving), and hemostatic therapy is the precise correction of the pathologic imbalance without overcompensating and thus creating safety issues. Unfractionated heparin is widely used as an anticoagulant, but is being replaced in many of its applications by currently available alternative parenteral agents such as the low molecular weight heparins and the direct thrombin inhibitors. These efficacious alternative agents offer advantages in terms of more predictable pharmacokinetics and improved safety, thereby reducing or eliminating the need for patient monitoring and reducing or eliminating the risk of heparin‐induced thrombocytopenia. Orally bioavailable direct thrombin and/or Factor Xa inhibitors now under development seem poised to become available over the next several years and will represent viable alternatives to both the parenteral anticoagulants and to warfarin, the only currently available oral anticoagulant. These agents promise the convenience of an oral drug without the need of intensive patient monitoring, as warfarin requires. Other therapeutic targets under current investigation for anticoagulation include Factor VIIa and Factor IXa. Antiplatelet agents such as aspirin, clopidogrel, and the parenteral GPIIb/IIIa antagonists are valuable and widely used drugs. New antiplatelet agents that act by already validated mechanisms (e.g., P2Y 12 receptor antagonism) or that act by mechanisms not targeted by current agents will also likely emerge in the not too distant future. Newer clot‐selective fibrinolytics have advantages over older agents such as streptokinase. Fibrinolytic agents still in development may offer further improvements in terms of safety and longer plasma half‐life.

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Anticoagulants, Antithrombotics, and Hemostatics

Bisacchi

2003

Burger's Medicinal Chemistry and Drug Discovery

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Argatroban use during pediatric interventional cardiac catheterization

Cetta

Graham

Wrona

et al. 2003

Cathet Cardio Intervent

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Argatroban is a synthetic direct thrombin inhibitor that does not interact with or induce heparin-dependent antibodies. It is approved for use in adults for prevention and treatment of thrombosis associated with heparin-induced thrombocytopenia (HIT). It has been administered safely in adults with HIT during coronary interventions. There are no reports of argatroban use for anticoagulation in pediatric patients. The present case describes the use of argatroban during coil embolization of a Fontan fenestration in a child with a history of HIT. The patient received a single bolus dose of 150 microg/kg of argatroban at the onset of the intervention. The fenestration was successfully occluded with a detachable coil. The activated clotting time (ACT) was > 200 sec throughout the procedure. The ACT returned to baseline 72 min after the bolus. No complications occurred. This case demonstrates the safe and successful use of argatroban during a transcatheter intervention in a pediatric patient with a history of HIT. The use of argatroban is promising for anticoagulation in children who require an alternative to heparin.

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