Indomethacin decreases furosemide-induced natriuresis and diuresis on the neonatal kidney.
Indomethacin is used to pharmacologically occlude patent ductus arteriosus in preterm infants. It induces renal untoward effects and furosemide is administered simultaneously to counteract them. The effect of furosemide is blunted by indomethacin. We analyzed comparatively the interactions of furosemide and indomethacin at the organic anion transport system in adult and newborn individuals. Adult and 5-day-old Wistar rats were allocated into three groups: (1) indomethacin (10 mg/kg, ip); (2) furosemide (2 mg/kg, ip); and (3) indomethacin/furosemide, at the same doses. Urinary flow, glomerular filtration rate (GFR), sodium and potassium fractional excretions, and free-water and osmolal clearances were estimated. Para-aminohippuric acid (PAH) uptake was measured in renal cortical slices to study the organic anion's secretory pathway. In adult and newborn rats, furosemide-induced increments in urinary fluxes and excretions of sodium and potassium were blunted by indomethacin administered simultaneously. PAH uptake was decreased to a further extent by indomethacin than by furosemide, suggesting that inhibition of the diuretic effect might be related to competition in the secretion of furosemide. Inhibitory interaction between indomethacin and furosemide was achieved at approximately 10-fold lower concentrations in the newborn than in the adult rats, suggesting that tubular secretion in the neonate is more sensitive to the action of these drugs than in the adult individual.
Reyes
Jose L
JL
Department of Physiology, Biophysics, and Neurosciences, Center for Research and Advanced Studies (CINVESTAV), Ave. Instituto Politecnico Nacional 2508, México City, D. F. 07360, Mexico. jreyes@fisio.cinvestav.mx
Aldana
Irma
I
Barbier
Olivier
O
Parrales
Arlen A
AA
Melendez
Estela
E
D000818:Animals; D000831:Animals, Newborn; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology; D004336:Drug Antagonism; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D009318:Natriuresis / Q000187:drug effects*; D009995:Osmosis; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine; D014556:Urine / Q000502:physiology; D014867:Water
D004232:Diuretics; D014867:Water; D005665:Furosemide; D012964:Sodium; D007213:Indomethacin