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  • Title: Clinical pharmacologic observations on timolol. II. Antihypertensive effect and kinetic disposition on twice-daily dosing in patients with mild or moderate hypertension.
    Author: Ishizaki T, Tawara K, Oyama Y, Nakaya H.
    Journal: J Clin Pharmacol; 1978; 18(11-12):519-29. PubMed ID: 721949.
    Abstract:
    Timolol given on a twice-daily schedule has shown both antihypertensive effectiveness and plasma renin-suppressing action in eight patients with mild or moderate hypertension. However, the causal relationship between the drug plasma level, blood pressure fall, and change in plasma renin activity was not so clearly demonstrated in the present study. The disposition profiles of timolol at the steady state show an elimination half-life of 4.7 +/- 0.7 hours and a total plasma clearance of 225 +/- 21 ml/min. These values are found to be different from those of our previous observations obtained in normal individuals. Although the range of mean timolol concentrations at steady state varies to a certain extent among different patients, the dosage regimens for patients who will receive treatment for certain chronic disease states (e.g., arrythmias, obstructive cardiomyopathy, and angina pectoris, but not hypertension) in relation to plasma levels should be based on the disposition data obtained under steady state conditions. Bronchospasm developed in one of eight patients whose timolol level was found to be higher than the average of other patients given the same dosage.
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