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, C1) were found in gentamicin-pretreated rabbits, the changes being dependent on the dose and schedule of administration. The most pronounced changes were those in digoxin kinetics during simultaneous 5-day treatment with digoxin (0.035 mg/kg i.v.) and nontoxic (10 and 2 mg/kg) doses of gentamicin. The toxicity of digoxin in guinea-pigs, assessed by administration of 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 either unchanged or 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; D002415:Cats; D004077:Digoxin / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000633:toxicity; D004347:Drug Interactions; D005260:Female; D005839:Gentamicins / Q000494:pharmacology*; D006168:Guinea Pigs; D007668:Kidney / Q000187:drug effects; D008297:Male; D009469:Neuromuscular Junction / Q000502:physiology; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects
D005839:Gentamicins; D004077:Digoxin