β-Blocking effects of timolol at low plasma concentrations

Autor: Lotta Salminen, Sakari Karhuvaara, Mika Scheinin, Esko Iisalo, Risto Huupponen, Timo Kaila, Pekka Havula
Rok vydání: 1991
Předmět:
Zdroj: Clinical Pharmacology and Therapeutics. 49:53-58
ISSN: 1532-6535
0009-9236
DOI: 10.1038/clpt.1991.10
Popis: The concentration-effect relationship of 0.25 mg intravenous timolol with and without pretreatment with 100 mg quinidine was studied in six healthy young volunteers with a randomized, double-blind, crossover study design. Blockade of cardiac beta-adrenoceptors was assessed by determining the dose ratios (DR) of isoproterenol infusions required to increase heart rate by 25 beats/min before and after timolol infusion. The logarithm of timolol concentration in plasma was linearly related to the logarithm (DR-1) of isoproterenol infusion, with a mean Pearson correlation coefficient of 0.89 +/- 0.11 (+/- SD; n = 24) at timolol concentrations well below 1 ng/ml. The increases in cyclic adenosine monophosphate (cAMP) and norepinephrine plasma levels caused by isoproterenol infusions were attenuated after timolol. Quinidine administration increased timolol plasma levels and cardiac beta-blocking effects by 10% to 40%. It was concluded that timolol at concentrations below 1 ng/ml in plasma competitively antagonizes cardiac and noncardiac effects of isoproterenol infusions. Timolol effects are augmented after quinidine administration. The beta-blockade occurring at low plasma levels can explain side effects and actions of ocularly applied timolol.
Databáze: OpenAIRE
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