Effect of dextran sulfate on renal accumulation of gentamicin.
The effect of dextran sulfate of three molecular weights (1000, 5000, and 90,000) on the accumulation of gentamicin in rat kidney was investigated using a continuous infusion technique. During the infusions of both gentamicin and gentamicin-dextran sulfate mixtures, the gentamicin plasma concentration was maintained at 10 microgram/ml. The renal cortical accumulation of gentamicin was significantly lower when dextran sulfate (1000, 5000) was coadministered. The inhibition of cortical gentamicin accumulation increased with increasing dextran sulfate dose, and it was proportional to the amount of dextran sulfate excreted into the urine. Analysis by electrophoresis on cellulose acetate membrane indicated that gentamicin binds to dextran sulfate in rat urine. Therefore, gentamicin-dextran sulfate binding within the lumen of the proximal tubules may reduce the renal reabsorption and possibly the renal toxicity of gentamicin.
Tokyo College of Pharmacy, Japan.
S
S
Kikuchi
Y
Y
Aramaki
H
H
Nonaka
S
S
Tsuchiya
D000818:Animals; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology* / Q000652:urine; D004588:Electrophoresis, Cellulose Acetate; D005839:Gentamicins / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains
D003911:Dextrans; D005839:Gentamicins; D016264:Dextran Sulfate