Timolol and atenolol: relationships between oxidation phenotype, pharmacokinetics and pharmacodynamics.
The pharmacokinetics and pharmacodynamics of atenolol and timolol were studied in six extensive and four poor metabolisers 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 less than 0.02). The mean of the AUC values for timolol was significantly greater in the poor metabolisers than in the extensive metabolisers (P less than 0.05). There was a significant correlation between the debrisoquine to 4-hydroxydebrisoquine ratio and beta-adrenoceptor blockade 24 h after dosing with timolol (rs = 0.66, P less than 0.05). The mean degree of beta-adrenoceptor blockade was significantly greater in the poor metabolisers than in the extensive metabolisers 24 h after dosing with timolol (P less than 0.01). There was no relation between the debrisoquine to 4-hydroxydebrisoquine ratio and the pharmacokinetics or pharmacodynamics of atenolol.
Lewis
R V
RV
Lennard
M S
MS
Jackson
P R
PR
Tucker
G T
GT
Ramsay
L E
LE
Woods
H F
HF
D000319:Adrenergic beta-Antagonists; D000328:Adult; D001262:Atenolol / Q000097:blood / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003647:Debrisoquin / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008297:Male; D010084:Oxidation-Reduction; D010641:Phenotype; D005082:Physical Exertion; D013056:Spectrophotometry, Ultraviolet; D013999:Timolol / Q000097:blood / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D001262:Atenolol; D013999:Timolol; D003647:Debrisoquin