Interaction of diclofenac and ketoprofen with cardioactive drugs in rats.
The interaction of diclofenac and ketoprofen, both applied intraperitoneally in a dose of 8 mg/kg for twenty-eight days, was assessed with cardioactive drugs in rats. Interaction was assessed on the basis of ECG records after the infusion of adrenaline, verapamil or lidocaine to the rats treated with diclofenac or ketoprofen vs control. The infusion time was measured in seconds to the moment of the appearance of the first heart reaction to the infusion of the cardioactive drug, then to the appearance of more frequent changes in the ECG record, and finally, to the occurrence of the toxic effect. It was also measured the plasma concentrations of sodium and potassium ions. As well as diclofenac and ketoprofen concentration, 2 hours after single and 28th dose. ECG patterns revealed no occurrence of cardiotoxic action of diclofenac and ketoprofen. The treatment with diclofenac caused significantly lower sodium plasma concentrations whereas the concentration of potassium was increased. Diclofenac concentrations were the same after a single and multiple doses, whereas concentrations of ketoprofen were significantly higher after a single dose than after its multiple applications.
Jakovljevic
V
V
Department of Pharmacology, Toxicology & Clinical Pharmacology, Faculty of Medicine, University Novi Sad, Republic of Serbia.
Sabo
A
A
Tomić
Z
Z
Milijasević
B
B
Popovic
M
M
Vasovic
V
V
Rasković
A
A
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology*; D004347:Drug Interactions; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D007660:Ketoprofen / Q000008:administration & dosage / Q000494:pharmacology*; D008012:Lidocaine / Q000494:pharmacology; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D002317:Cardiovascular Agents; D014662:Vasoconstrictor Agents; D004008:Diclofenac; D007660:Ketoprofen; D008012:Lidocaine; D012964:Sodium; D014700:Verapamil; D011188:Potassium; D004837:Epinephrine