title: Effects of phenobarbital and tobacco smoking on furosemide kinetics and dynamics in normal subjects.
abstract: 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 less than 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.
mesh_terms: D000293:Adolescent; D000328:Adult; D005665:Furosemide / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D010634:Phenobarbital / Q000097:blood / Q000494:pharmacology*; D012907:Smoking; D012964:Sodium / Q000652:urine
chemical_list: D005665:Furosemide; D012964:Sodium; D010634:Phenobarbital