Effect of two diuretics on amikacin pharmacokinetics in dogs

Amikacin is a relatively new aminoglycoside antibiotic which has exhibited a wide spectrum of activity against many gram-negative bacteria. Amikacin has shown the potential to produce toxicity - especially ototoxicity and nephrotoxicity. The package insert of the antibiotic warns that concurrent administration of potent, intravenous diuretics enhances aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue. The purpose of this study was to determine if two potent intravenous diuretics, furosemide and ethacrynic acid, effect the pharmacokinetic parameters of amikacin in such a manner as to indicate that the amikacin concentrations in tissue and serum are altered. Specific tissue or fluid amikacin concentrations other than serum were not assessed in the study; however, the antibiotic concentrations in hybrid tissue groupings termed the central and peripheral compartments were determined over a period of time. Since serum has been shown to be part of the central compartment, amikacin concentration in serum at any time reflected antibiotic concentration for all tissues of the central compartment. [...]