Effects of interactions between drugs on the renal excretion of trientine in rats--acetazolamide and furosemide increase trientine excretion.
OBJECTIVE
To elucidate the effects of drug interactions on the urinary excretion of trientine in rats.


METHODS
Trientine and various other drugs were intravenously administered to rats and the urinary excretion of trientine was investigated. To clarify the mechanisms of drug-drug interactions, we also investigated the effects of various drugs on spermine uptake by rat renal brushborder membrane vesicles.


RESULTS
Cimetidine, a substrate of the H+/organic cation antiporter, and aminoglycoside antibiotics did not affect trientine excretion, while acetazolamide and furosemide, which increase the concentration of sodium ions in renal proximal tubules, increased the excretion of trientine. However, trichlormethiazide, which acts in renal distal tubules, did not affect trientine excretion. Acetazolamide and furosemide did not directly affect the Na+/spermine transporter because these diuretics had no effect on the uptake of spermine into the rat renal brush-border membrane vesicles.


CONCLUSIONS
There is no interaction between trientine and the substrate of the H+/organic cation antiporter or aminoglycoside antibiotics. However, drugs that change the concentration of sodium ions in renal proximal tubules, such as diuretics, can increase the trientine excretion since the increase in the luminal concentration of sodium ion accelerates the Na+/spermine antiporter.
Kobayashi
M
M
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
Fujisaki
H
H
Sugawara
M
M
Iseki
K
K
Miyazaki
K
K
D000086:Acetazolamide / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004232:Diuretics / Q000494:pharmacology*; D004347:Drug Interactions; D005665:Furosemide / Q000494:pharmacology*; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014266:Trientine / Q000008:administration & dosage / Q000652:urine*
D004232:Diuretics; D005665:Furosemide; D000086:Acetazolamide; D014266:Trientine