A MODEL TO DESCRIBE MYOCARDIAL DRUG DISPOSITION IN THE DOG
- 1 January 1980
- journal article
- research article
- Vol. 214 (1) , 31-36
Abstract
A model, employing open-chested, anesthetized dogs, was developed to facilitate the study of myocardial drug disposition. Propranolol was used as a model compound for initial investigation. Propranolol was administered as a single i.v. bolus of 0.5 mg/kg or by a stepwise infusion protocol employing 3 rates: 2.6, 6.5 and 12.0 .mu.g/kg per min. Blood and myocardial biopsy samples were obtained at specified times and the concentration of propranolol in tissue homogenates and plasma was determined by a high-pressure liquid chromatographic procedure. The concentration-time data obtained from the i.v. bolus studies were fitted to a 3-compartment model where 1 of the compartments represented the myocardium. The model predicts that plasma and myocardial concentrations achieve distribution equilibrium within 2 min after administration. The myocardial-to-plasma concentration ratios ranged from 6.2-20.3 and were constant with time for each dog. The myocardial-to-plasma concentration ratios remained constant during the infusion protocol, indicating linear accumulation up to myocardial concentrations of 6.7 .mu.g/ml. To assess regional myocardial concentration differences, the concentration of drug in the right atrium was compared with the concentration in the left ventricle at the end of the infusion protocol. The concentrations were not significantly different. The model developed will be used to study the myocardial disposition of several antiarrhythmic drugs and the factors which affect their rate and extent of accumulation.This publication has 6 references indexed in Scilit:
- Role of concentration-dependent plasma protein binding in disopyramide dispositionJournal of Pharmacokinetics and Biopharmaceutics, 1979
- Biological determinants of propranolol disposition in manClinical Pharmacology & Therapeutics, 1978
- Physiologically Based Pharmacokinetic Model for Digoxin Distribution and Elimination in the RatJournal of Pharmaceutical Sciences, 1977
- STUDIES ON UPTAKE AND BINDING OF PROPRANOLOL BY RAT TISSUES1977
- UPTAKE OF PROPRANOLOL BY ISOLATED GUINEA-PIG ATRIA1967
- Tissue concentration and turnover of tritiated digoxin in dogsThe American Journal of Cardiology, 1966