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.
Staneva-Stoytcheva
D
D
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Kristeva
E
E
Prodanova
K
K
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002682:Chinchilla; D004077:Digoxin / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D004347:Drug Interactions; D005839:Gentamicins / Q000493:pharmacokinetics / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D008297:Male; D011817:Rabbits; D011863:Radioimmunoassay; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D005839:Gentamicins; D007457:Iodine Radioisotopes; D004077:Digoxin; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium