Timolol and atenolol: relationships between oxidation phenotype, pharmacokinetics and pharmacodynamics.

Abstract

The pharmacokinetics and pharmacodynamics of atenolol and timolol were studied in 6 extensive and 4 poor metabolizers of debrisoquine. There was a significant correlation between the debrisoquine to 4-hydroxydebrisoquine ratio and the area under the plasma concentration time curve (AUC) for timolol (rs = 0.75, P < 0.02). The mean of the AUC values for timolol was significantly greater in the poor metabolizers than in the extensive metabolizers (P < 0.05). There was a significant correlation between the debrisoquine to 4-hydroxydebrisoquine ratio and .beta.-adrenoceptor blockade [reduction in post-exercise heart rate] 24 h after dosing with timolol (rs = 0.66, P < 0.05). The mean degree of .beta.-adrenoceptor blockade was significantly greater in the poor metabolizers than in the extensive metabolizers 24 h after dosing with timolol (P < 0.01). There was no relation between the debrisoquine to 4-hydroxydebrisoquine ratio and the pharmacokinetics or pharmacodynamics of atenolol.