Abstract
The relationship between pharmacokinetics and pharmacodynamics was studied in dogs using sotalol as a model. The t 1/2 of this drug (4.30 +/- 0.40 hr) in dogs was longer than that of other beta adrenergic blockers. The renal clearance of the drug (4.21 +/- 0.31 ml/min/kg) was approximately 90% of total plasma clearance together with an extensive fraction excreted unchanged (72 +/- 12% of dose) in urine. Significant beta blockade, assessed by the response to isoproterenol tachycardia, was observed without change in blood pressure during the experiments. The log plasma sotalol concentration correlated significantly with the beta blockade (P less than .001). In an attempt to obtain insight into drug concentration-effect-time data, we applied a theory for correlating the observed kinetic data with the pharmacological effects using the elimination rate constant (beta) and the slope of log concentration-effect relationship (m). The rate of decline of drug effects (Rd) derived from this application agreed well with that actually observed in the effect-time interrelations.
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Relationship between pharmacokinetics and pharmacodynamics of the beta adrenergic blocking drug sotalol in dogs.
