Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin

Some pharmacokinetic and pharmacodynamic interactions between digoxin and gentamicin were studied in experiments on rabbits, guinea-pigs and cats. An increase of digoxin serum levels and changes in some basic pharmacokinetic parameters of digoxin (t1/2 alpha, t1/2 beta, AUC, AL) were established in gentamicin-pretreated rabbits, the changes being dependent on the dose and schedule of administration. Most pronounced were the changes in digoxin kinetics during simultaneous 5-day treatment with digoxin (0.035 mg/kg i. p.) and nontoxic doses (10 and 2 mg/kg) of gentamicin. The toxicity of digoxin in guinea-pigs, assessed by lethal doses of digoxin, was increased only after the highest dose of gentamicin (100 mg/kg), while after nontoxic or close to therapeutic doses (10 and 2 mg/kg) of gentamicin the digoxin toxicity was not changed or was even decreased. Digoxin decreased the nerve-muscle blocking effect of gentamicin on cat ischiadicus-gastrocnemius preparation. The possible mechanisms involved are discussed.