Effects and interactions of gentamicin, polyaspartic acid and diuretics on urine calcium concentration.
Gentamicin causes isolated, reversible calciuria in rats by an unknown mechanism. We hypothesized that gentamicin calciuria is related to nonantibacterial properties that may interfere with transtubular calcium transport (calcium channel blockade, Na,K-ATPase inhibition or competition with calcium for binding to the brush-border membrane). The calciuric effect of gentamicin was compared to the calcium channel blockers lanthanum and cobalt, the Na,K-ATPase inhibitor ouabain and the polycation aprotinin (which competes with gentamicin for brush-border membrane binding). Although gentamicin 0.02 mmol/kg caused a 6-8-fold increase in urine calcium concentration, none of the other agents was calciuric. We also found that the calciuric effects of gentamicin and furosemide were additive, whereas the noncalciuric diuretic chlorothiazide had no effect on gentamicin calciuria. We also determined the effect of poly-L-aspartic acid (PAA), which binds gentamicin and prevents nephrotoxicity. PAA caused isolated calciuria similar in magnitude and character to gentamicin. However, PAA pretreatment decreased the magnitude of gentamicin calciuria to insignificance. PAA pretreatment did not prevent furosemide calciuresis. These results indicate that: 1) gentamicin and furosemide calciuria are caused by different mechanisms; 2) gentamicin calciuria is probably not mediated by calcium channel blockade, Na,K-ATPase inhibition or displacement of brush-border membrane-bound calcium; 3) gentamicin and PAA calciuria may reflect interference with intracellular events related to transtubular calcium transport.
Elliott
W C
WC
Department of Medicine, State University of New York at Syracuse, USA.
Patchin
D S
DS
D000818:Animals; D002118:Calcium / Q000652:urine*; D004232:Diuretics / Q000494:pharmacology*; D004347:Drug Interactions; D005665:Furosemide / Q000494:pharmacology; D005839:Gentamicins / Q000494:pharmacology*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000652:urine; D051381:Rats; D011916:Rats, Inbred F344; D012964:Sodium / Q000652:urine; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
D004232:Diuretics; D005839:Gentamicins; D010455:Peptides; C017645:polyaspartate; D005665:Furosemide; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium