Disposition and absolute bioavailability of furosemide in healthy males.

Furosemide (40 mg) was administered to 18 healthy adult males as an intravenous dose, an oral solution, and in tablet form. The pharmacokinetics of intravenous furosemide were studied, determining a total body clearance rate of 117.6 +/- 41.3 ml/min and a harmonic mean half-life of 78 min. The mean absolute bioavailability determined by ratio of areas under the plasma-time curves was 64 and 71% for the solution and tablet, respectively. The mean absolute bioavailability determined by the ratio of urinary cumulative excretion data was 61 and 66% for the solution and tablet, respectively. The absolute bioavailability of furosemide determined with plasma and urine data were not significantly different. Thus, urine data alone may be used to establish bioavailability of furosemide. Inspection of plasma-time curves revealed secondary maxima in several subjects, suggesting enterohepatic cycling.

The effect of probenecid on nafcillin disposition.

Five normal male volunteers participated in an open crossover study designed to examine the disposition of nafcillin given intravenously with and without probenecid. Each subject received two 500 mg iv doses of sodium nafcillin seven days apart, one dose without probenecid and another dose during oral probenecid administration of 1.0 Gm at bedtime prior to the study day and 1.0 Gm two hours before the nafcillin dose. Blood and urine samples were collected for 10 hours after nafcillin dosing. Assay for nafcillin concentrations was performed via the cup-plate technique with M. luteus. Administration of probenecid significantly increased and prolonged circulating plasma concentrations of nafcillin. Probenecid administration significantly, decreased the per cent of nafcillin recovered in the urine (30% vs. 16.9%). Probenecid pretreatment increased the ana under the plasma drug concentration-time curve (AUC) two-fold and decreased the total body clearance significantly with decreases in both renal and non-renal clearance. K12/k21 and Vc did not significantly change with probenecid. Because probenecid coadministration did not appear to change nafcillin distribution while increasing and prolonging plasma concentrations, probenecid can be recommended to be given concurrently when high nafcillin plasma concentrations are desirable. Changes in plasma concentrations are apparently due to alterations in both renal and non-renal clearances of nafcillin.