THE RELATIONSHIP BETWEEN PHARMACOKINETIC VARIABLES AND PHARMACODYNAMIC PROFILES OF BOLUS VERSUS CONTINUOUS INFUSION OF FUROSEMIDE IN CRITICALLY ILL PATIENTS

In this investigation, the pharmacokinetic variables of continuous infusion and intermittent bolus injectionof furosemide and the possible relationship between its pharmacokinetic characteristics andpharmacodynamic profile among intensive care unit (ICU) patients were studied.In this prospective, randomized, clinical trial, twelve patients received IV bolus of 20 mg of the drugduring 3 hours period and, the drug dose was doubled, when the urine output was less than 1 ml/kg/h(group 1). The other nine patients received a continuous intravenous furosemide infusion at the rate of 0.1mg/kg/h (group 2). The amount of furosemide in serum was measured by high performance liquidchromatography (HPLC).Results showed a positive correlation between plasma clearance of furosemide and its diuretic activity(P=0.01). The pharmacokinetic parameters such as Vd (l), CL (ml/min), Ke (min-1) and t½ (min) incontinuous infusion patients were not significantly differed from the bolus patients (P-values 0.5, 0.9, 0.9,0.9, respectively). Nevertheless the observed plasma clearance of drug in the continuous infusion groupwas clinically higher than bolus injection group and as a result the cumulative urine output per hour permg of furosemide in a continuous infusion was observed to be higher than bolus(P=0.2). Changes inserum sodium and potassium were similar for both groups, but bolus injection patients were associatedwith higher potassium depletion (P=0.001). Therefore, continuous infusion seems to be better means ofdiuretic therapy in critically ill patients.