[The mechanism of the renal excretion of disopyramide in rats. I].
The mechanism involved in the renal excretion of disopyramide (DPM) is still incompletely understood. The purpose of this study was to examine the renal handling of DPM and the interactions between DPM and several organic anionic or cationic drugs related to the renal tubular secretion, using the renal clearance and renal cortical slices uptake techniques in rats. The clearance ratio of DPM was greater than that of glomerular filtration and this suggests the tubular secretion of DPM. The clearance ratio of DPM did not change after infusion of either anionic drugs (p-aminohippurate and probenecid) or a cationic drug (cimetidine). The results of time and concentration-dependent experiments using renal cortical slices demonstrated that DPM was accumulated against a concentration gradient by a saturable process. Inhibition of uptake by 2,4-dinitrophenol and cyanide indicated an energy dependence. DPM uptake was considerably inhibited by the cationic drugs, cimetidine and quinine, suggesting that DPM was transported by the cation transport mechanism. Probenecid, a competitor for the anion transport mechanism, moderately inhibited DPM uptake.
Ito
T
T
Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
Takahashi
Y
Y
Tomidokoro
K
K
Nishino
T
T
Fukuzawa
Y
Y
Chiba
K
K
Miyazaki
S
S
Takada
M
M
D000818:Animals; D002404:Catheterization; D004206:Disopyramide / Q000008:administration & dosage / Q000652:urine*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D004206:Disopyramide