Relationship between pharmacokinetics and pharmacodynamics of the beta adrenergic blocking drug sotalol in dogs
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 to...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 211; no. 2; pp. 331 - 337 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.11.1979
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Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3565 1521-0103 |