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Transdermal Timolol: β Blockade and Plasma Concentrations After Application for 48 Hours and 7 Days
Author(s) -
McCrea Jacqueline B.,
Vlasses Peter H.,
Franz Thomas J.,
Zeoli Laura
Publication year - 1990
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1990.tb02585.x
Subject(s) - timolol , transdermal , heart rate , pharmacokinetics , pharmacodynamics , plasma concentration , medicine , anesthesia , blockade , chemistry , pharmacology , endocrinology , blood pressure , intraocular pressure , surgery , receptor
An effective and well‐tolerated transdermal β‐adrenergic blocker that could be applied once weekly would facilitate compliance. The pharmacokinetics and pharmacodynamics of a once‐weekly formulation of transdermal timolol, a β‐blocker, were evaluated in healthy males. One (n = 6), two (n = 5), and three (n = 5) patches (97.5 mg base/12.58‐cm 2 patch) were applied at weekly intervals to the subjects' inner arm for 48 hours (part A) and two patches were applied for 7 days (part B). In part A, mean exercise (bicycle ergometry) heart rate (beats/min, bpm) was suppressed from baseline at 48 hours after the patch (p < 0.05) in each case (1 patch 167 vs 131 bpm; 2 patches 165 vs 120 bpm; 3 patches 159 vs 120 bpm). Mean plasma timolol concentrations at 48 hours after the patch for one, two, and three patches were 5, 11, and 14 ng/ml, respectively. For part B, mean exercise heart rate at baseline, 24, and 168 hours was 161, 113, and 130 bpm (p < 0.05), and mean plasma timolol concentrations at these times were 0, 23, and 4 ng/ml. The relationship between suppression of exercise heart rate and plasma timolol concentrations within subjects was well described by an inhibitory E MAX model, where E MAX ranged from a suppression of 42–65 bpm associated with a 50% inhibitory (IC 50 ) concentration that ranged from 2–4 ng/ml. Transdermal timolol was associated with significant B blockade for up to 7 days, and caused only minimal skin irritation.