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Dose‐dependent urinary excretion of chlorthalidone
Author(s) -
Fleuren Harry L. J.,
Wissen Corrien Verwey-van,
Rossum Jacques M.
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1979256806
Subject(s) - chlorthalidone , pharmacokinetics , urinary system , chemistry , renal function , dose–response relationship , renal physiology , excretion , crossover study , plasma concentration , endocrinology , diuretic , medicine , pharmacology , urology , placebo , alternative medicine , pathology
Renal excretion, plasma concentration, and erythrocyte concentration profiles of chlorthalidone were studied in 17 healthy human subjects for 100 to 200 hr after oral administration of single doses of 50, 100, or 200 mg. Three subjects received all three doses in a crossover design. The other 14 were involved in the study at one dosage level. The 50‐mg dose was taken altogether by 6 subjects, the 100‐mg dose by 11, and the 200‐mg dose by 6. Total urinary recovery of chlorthalidone extrapolated to infinity was 44.4% of the 50‐mg dose (22.2 ± 3.4 mg), 43.1% of the 100‐mg dose (43.1 ± 4.7 mg), but only 29.0% of the 200‐mg dose (58.0 ± 9.7 mg; mean values ± SD). There was a large interindividual variation in the renal plasma clearance of chlorthalidone (52 to 125 ml/min after 50 mg, 43 to 107 ml/min after 100 mg, and 47 to 77 mllmin after 200 mg). This variation correlated more with differences between subjects in the area under the plasma concentration curve than with those in total urinary recovery of the drug. The subjects available for between‐dose comparison showed an average decrease of 27% in renal clearance in going from the single 50‐mg to the 200‐mg dose, suggesting a causal relationship with the limited urinary recovery of the drug at the higher dose. These pharmacokinetic results indicate that the known antihypertensive dose‐response curve of chlorthalidone in man may well be related to the extent of its urinary recovery.