A study on furosemide disposition in man.

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Abstract
Furosemide disposition in man was studied. Six male young healthy volunteers were given 20 mg furosemide by bolus intravenous injection and 10, 20, 30 and 40 mg furosemide (solution) orally. The serum drug concentration was determined by high performance liquid chromatography and the urinary excretion was determined spectrophotometrically after diazotization. The experimental data from serum and urine samples were simultaneously subjected to computer analysis. On the basis of the results, it was demonstrated that disposition of furosemide in man can be described by a two-compartment open model with the following average parameters: t1/2.alpha. = 0.237 .+-. 0.069 ha, t1/2.beta. = 1.29 .+-. 0.20 h and Vss = 8.46 .+-. 2.17 l. After oral administration of furosemide solution, the drug was rapidly absorbed from the gastrointesitnal tract with a first-order absorption rate constant ka of 2.33 .+-. 0.93 h-1 but there was a lag time of about 6.45 min for drug resolution and entering the absorption site. The oral relative bioavailability was estimated as 83 .+-. 14%, which was higher than reported values. The elimination of furosemide was very rapid and was mainly via the renal route. The systemic clearance (CLs) and renal clearance (CLr), following bolus intravenous dosing were 7.60 .+-. 2.29 and 6.44 .+-. 1.18 l/h, respectively. The oral route did not influence CLs and CLr on the whole, but the nonrenal clearance ratio (CRnr) after oral dosing (15.7 .+-. 4.8%) was significantly higher than that after intravenous administration (11.2 .+-. 4.0%), which can be explained by a first-pass effect of the liver-portal system.