Effects of phenobarbital and tobacco smoking on furosemide kinetics and dynamics in normal subjects

This study was carried out to determine whether furosemide (F) kinetics and dynamics were influenced by phenobarbital and tobacco smoking. Our subjects were 10 normal men: five nonsmokers (NS) and five smokers (S). They received a single intravenous F injection of 40 mg. Regular serum and urine collections were made. In a second study, the NS group received 100 mg phenobarbital orally for 15 days and then a second dose of F. Cumulative 8‐hr urinary excretion of sodium was identical for NS, NS with phenobarbital, and S at 345 ± 30, 357 ± 29, and 353 ± 25 mmol. Diuresis was smaller by 800 ml (20%) in S than in NS. F increased endogenous creatinine clearance from 117 ± 13 to 196 ± 17 ml/min in NS and from 110 ± 12 to 222 ± 30 ml/min in NS with phenobarbital. In the S group, endogenous creatinine clearance showed a tendency to increase only slightly, from 136 ± 23 to 180 ± 34 ml/min. The increase in free water clearance caused by F was smaller in the S group than in the NS group (P < 0.05). Protein binding and distribution of F were not affected by phenobarbital or tobacco smoking. F clearance was slightly higher in S than in NS, which was primarily the result of a slight increase in extrarenal F clearance. In the NS group, F clearance remained constant after phenobarbital. It is concluded that tobacco smoking in normal subjects affects the diuretic response to F without modifying kinetics. Clinical Pharmacology and Therapeutics (1983) 34 , 170–175; doi: 10.1038/clpt.1983.148