No abstract

Argatroban, a direct thrombin inhibitor, is approved in the United States in adults as an anticoagulant for prophylaxis or treatment of thrombosis in heparin-induced thrombocytopenia (HIT) and in adults with or at risk for HIT undergoing percutaneous coronary intervention. The authors conducted a literature analysis to characterize the uses, dosing patterns, and safety of argatroban anticoagulation in pediatric patients. A comprehensive literature search identified nine articles describing 34 patients aged 1 week to 16 years who received argatroban anticoagulation for prophylaxis or treatment of thrombosis, cardiac catheterization, hemodialysis, extracorporeal membrane oxygenation or ventricular assist device support, or cardiopulmonary bypass. Most (85%) patients had HIT, a history of HIT, and/or HIT antibodies. For HIT thromboprophylaxis or treatment, argatroban dosing varied widely (0.1-12 mcg/kg/min), with no obvious relationship between patient age and dosage requirement. Overall, in these pediatric patients, therapeutic levels of anticoagulation were achieved despite the wide range of doses used. For pediatric patients undergoing cardiac catheterization, argatroban doses lower than those recommended in adults appeared to provide therapeutic anticoagulation. There was an unacceptably high bleeding risk with argatroban anticoagulation during pediatric cardiopulmonary bypass. Due to the limitations of case reports and/or case series, prospective studies with pharmacokinetic analyses are needed to evaluate the use of argatroban in pediatric patients.

No abstract

Fenoldopam, a dopamine agonist, was evaluated in renal clearance studies during water diuresis after oral doses of 25, 50, and 100 mg. After the 100-mg dose there was an increase in urine flow rate, paraaminohippurate clearance, free water clearance, and an increase in the fractional excretion of sodium, calcium, and uric acid. These effects were evident within the first hour, peaked during the second hour, and lasted about 3 hr. Doses of 50 and 25 mg induced smaller increases. There was no significant change in inulin clearance at any dose. To elucidate the mechanism of action, the studies were repeated after treatment with a dopamine-receptor antagonist (metoclopramide). Metoclopramide greatly diminished the renal effects of fenoldopam. These findings indicate that fenoldopam is an active renal vasodilator in man and increases urine volume, free water clearance, and fractional excretion of sodium by stimulation of renal dopamine receptors.