Τίτλος:
H3 propranolol serum levels following lidocaine administration in rats with CCL4 - induced liver damage
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Liver disease alters the pharmacokinetic and pharmacodynamic properties of hepatically eliminated drugs. The main factors influenced are plasma albumin levels, enzyme balance (induction & inhibition) and drug binding to tissue proteins. The influence of lidocaine on serum, heart and liver propranolol levels in Wistar rats after liver injury induced by carbon tetrachloride CCl4 0.4 ml/kg × 2/wkl, was investigated. 40 male Wistar rats were divided into four groups (I, II, III, IV; n=10), Group I animals received only propranolol (labelled + cold substance) 40 mg/kg/12 h p.o., group II propranolol plus lidocaine in a single dose of 4mg/kg s.c., group III was treated with CCl4 for 6 weeks and received propranolol ×2 at the same dosage as group I, while group VI was treated with CCl4 and the same drug dosage as group II. The simultaneous administration of H 3-propranolol and lidocaine increased propranolol levels in the serum and tissues. The liver in damaged animals showed an increase of propranolol level under lidocaine co-administration, probably due to CCl4 - induced liver enzyme activity, resulting in a rapid propranolol metabolism or to competition between both drug protein binding sites. The increased propranolol levels in the heart after lidocaine administration were probably due to attributed to its high affinity for heart tissue. Consequently, as regards the therapeutic approach for patients with liver disease receiving propranolol their propranolol dosage should be reduced when lidocaine is co-administered.
Συγγραφείς:
Kotsiou, A.
Tsamouri, M.
Anagnostopoulou, S.
Tzivras, M.
Vairactaris, E.
Tesseromatis, C.
Περιοδικό:
European Journal of Drug Metabolism and Pharmacokinetics
Εκδότης:
Editions Medecine et Hygiene
Λέξεις-κλειδιά:
carbon tetrachloride; lidocaine; propranolol; antiarrhythmic agent; beta adrenergic receptor blocking agent; carbon tetrachloride; lidocaine; propranolol; tritium, animal experiment; animal model; animal tissue; article; controlled study; drug blood level; drug metabolism; drug potentiation; drug protein binding; enzyme activity; heart; liver; liver injury; male; nonhuman; rat; animal; blood; chemically induced disorder; comparative study; drug effect; drug interaction; experimental liver cirrhosis; heart muscle; liver; metabolism; pathology; Wistar rat, Adrenergic beta-Antagonists; Animals; Anti-Arrhythmia Agents; Carbon Tetrachloride; Drug Interactions; Lidocaine; Liver; Liver Cirrhosis, Experimental; Male; Myocardium; Propranolol; Rats; Rats, Wistar; Tritium
