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Pharmacodynamics and Physicochemical Properties of Sotalol and Propranolol

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The researcher states that Propranolol is highly lipophilic and completely absorbed in the gastrointestinal tract. The bioavailability of the drug is more after food and when administered chronically. The distribution of the drug is very rapid. The pharmacokinetics studies have confirmed that they have a high binding affinity with the plasma. At the same time, the binding capability differs with the half-life  of the drug. The plasma protein binding of propranolol may affect the rate of excretion and hepatic clearance in animals including dogs and rats. The half-life of the drug is largely dependent on the liver blood flow.

Studies of intravenous administration in rats showed that higher concentrations of propranolol produced a reduced binding affinity for propranolol. At high doses, the half-life of the drug and the volume of distribution were found to be high. The half-life of the Sotalol in dogs was 4.3 ± 0.4 hours and this is longer than any other beta-adrenergic blocker in dogs. The renal clearance of the drug was 4.21 ± 0.31 ml/ min/ kg in dogs. The total plasma clearance was around 90% and 72 ± 12 % of the drug was excreted unchanged in urine.

Distribution and elimination of the drug follow first-order kinetics and the drug is excreted by the kidney. The total absorption of the drug orally was around 75- 90%. Sotalol is eliminated by the urine as unchanged drug up to a concentration of 90 +/- 12% in urine. On the other hand, propranolol was highly metabolized in the liver. The hepatic clearance of the drug from the whole body was around 65 – 103%. The drug is completely absorbed and hence it is not eliminated as the unchanged drug from the body through urine.

In monkeys, propranolol was completely absorbed and the plasma concentrations were observed after 1 hour. The excretion of the drug was completely through urine in a monkey, but in dogs and rats, 25% of the excretion was in the feces. When drug concentration was observed through HPLCS, the basic metabolites were present in the concentration of 35± 1% in dog, the  through  ± 2% in rats, and 53± 5% in the hamster.

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