No effect of probenecid on the renal and biliary clearances of digoxin in man.
1. The cardiac glycoside digoxin is subject to a number of pharmacokinetic interactions. This study concerns the influence of the anionic transport inhibitor probenecid on the steady-state kinetics of digoxin. 2. Six healthy young men were enrolled in the study. After an administration period of 6 days with digoxin only (0.5 to 1 mg p.o. day-1) or digoxin in combination with probenecid (2 g p.o. day-1; 8 days), digoxin was administered intravenously (0.7 oral dose) on day 7. Plasma and urine samples were taken over 48 h. The biliary clearance of digoxin was measured during day 8 by a duodenal perfusion technique. 3. Probenecid did not affect the plasma clearance (mean +/- s.d.: 255 +/- 80 vs 266 +/- 40 ml min-1), renal clearance (166 +/- 17 vs 155 +/- 10 ml min-1), biliary clearance (106 +/- 40 vs 111 +/- 50 ml min-1), elimination half-life (34.4 vs 35.2 h) or volume of distribution (538 +/- 241 vs 566 +/- 60 l) of digoxin. 4. Our results suggest that different systems exist in man for the renal and biliary secretion of probenecid and digoxin.
Hedman
A
A
Department of Clinical Pharmacology, Karolinska Institute, Huddinge University Hospital, Sweden.
Angelin
B
B
Arvidsson
A
A
Dahlqvist
R
R
D000284:Administration, Oral; D000328:Adult; D001659:Biliary Tract / Q000187:drug effects* / Q000378:metabolism; D004077:Digoxin / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D011339:Probenecid / Q000097:blood / Q000494:pharmacology*
D004077:Digoxin; D011339:Probenecid