Effects of quinidine on the renal tubular and biliary transport of digoxin: in vivo and in vitro studies in the dog.
Quinidine is known to inhibit the renal clearance of digoxin without affecting glomerular filtration rate. The renal interaction between these drugs was investigated by a combination of in vivo and in vitro methods. The uptake of digoxin by brush border membrane vesicles was not affected by quinidine. Similarly, digoxin did not inhibit the uptake of the cation N-methylnicotinamide by these vesicles and did not alter the binding kinetics of digoxin to the Na+, K+-adenosine triphosphatase by the antiluminal membrane vesicles. By using the in vivo multiple indicator dilution technique transtubular transport of digoxin was documented; renal-artery infusion of quinidine did not affect the recovery of digoxin in the renal vein or urine. Clearance studies documented that the decrease in the renal clearance of digoxin is paralleled by a significant fall in renal blood flow evidenced by a decrease in p-aminohippuric acid clearance. It is concluded that quinidine inhibits the renal excretion of digoxin not by competition at the tubular cell membrane level, but rather by decreasing renal blood flow. A parallel decrease in biliary clearance of digoxin is documented and may suggest a similar mechanism.
Koren
G
G
Division of Clinical Pharmacology, Hospital for Sick Children, Ontario, Canada.
Klein
J
J
Giesbrecht
E
E
Ben Dayan
R
R
Soldin
S
S
Sellers
E
E
MacLeod
S
S
Silverman
M
M
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D004077:Digoxin / Q000493:pharmacokinetics*; D004285:Dogs; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008871:Microvilli / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology*
D004077:Digoxin; D011802:Quinidine