In vitro-In vivo Drug Interaction Study of Paracetamol and Propranolol Hydrochloride

Introduction: Propranolol Hydrochloride is a non-cardio selective beta-adrenergic antagonist, used in the treatment or prevention of many disorders, including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism and migraine. Paracetamol is an antipyretic agent which is also known for its analgesia and is concurrently administered to patients who are on treatment with propranolol hydrochloride in the management of migraine. Objective: In the present work, an in vitro and in vivo drug interaction was assessed to establish the relationship between drug dissolution and plasma drug concentration and pharmacokinetics of selected drugs. Method: In vitro drug release studies were performed in simulated gastric juice (pH 1.2). The in vitro drug dissolution and changes in plasma concentration of the drugs in vivo in Wistar rats were determined individually and in the presence of other drug at different time interval. Results: A significant delay in the dissolution of propranolol hydrochloride in the presence of paracetamol was observed and the paracetamol dissolution was prolonged in the presence of propranolol hydrochloride. tmax of propranolol Hydrochloride was prolonged and extended t1/2 was found when propranolol hydrochloride was administered with paracetamol concurrently. A delay in tmax of paracetamol and shortened t1/2 was observed. Conclusion: The results show the existence of correlation between in vitro drug dissolution and in vivo plasma concentration and the corresponding pharmacokinetics of propranolol hydrochloride and paracetamol.