Effects of propranolol or paracetamol on lidocaine concentrations in serum and tissues.
OBJECTIVE
The goal of this study was to determine the interaction of lidocaine after paracetamol or propranolol administration.


METHODS
Group A rats received a mixture of cold lidocaine and (14)C lidocaine into the masseter muscle. Group B rats received lidocaine and paracetamol 7.5 mg/kg orally, whereas group C received lidocaine intramuscularly and propranolol 1.5 mg/kg orally. Five consecutive doses were administered. The levels of these drugs were estimated in serum and the total concentration and the percent protein binding of lidocaine in tissues (liver and mandible) were determined. The rats were killed 2 hours after the last dose.


RESULTS
The results suggest that lidocaine concentrations in serum were significantly increased after either paracetamol or propranolol administration. Additionally, the combined therapy of propranolol and lidocaine resulted in a significant decrease in the total concentration and the percent protein binding of lidocaine in tissues.


CONCLUSIONS
The coadministration of lidocaine with paracetamol or propranolol interferes with the metabolic profile, resulting in pharmacokinetic interactions that may be significant for the determination of the correct dose of lidocaine in clinical applications.
Department of Pharmacology, Medical School, University of Athens, Athens, Greece.
Theodosios
T
Saranteas
Costas
C
Mourouzis
Fanny
F
Koumoura
Christina
C
Tesseromatis
D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D004347:Drug Interactions; D007273:Injections, Intramuscular; D008012:Lidocaine / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D008334:Mandible / Q000378:metabolism; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D013223:Statistics as Topic; D014018:Tissue Distribution
D000319:Adrenergic beta-Antagonists; D018712:Analgesics, Non-Narcotic; D000779:Anesthetics, Local; D000082:Acetaminophen; D008012:Lidocaine; D011433:Propranolol