期刊
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
卷 55, 期 6, 页码 518-525出版社
BLACKWELL PUBLISHING LTD
DOI: 10.1046/j.1365-2125.2003.01796.x
关键词
hypertensive patients; centrally acting antihypertensive; saccadic eye movements; tolerance
Objectives The primary aim was to demonstrate that moxonidine, given in an experimental sustained release (SR) formulation, had no clinically relevant central nervous system (CNS) effects after 4 weeks of treatment. A clinically relevant CNS effect was predefined as more than 45degrees s(-1) reduction in saccadic peak velocity (SPV), corresponding to the effects of one night's sleep deprivation. Methods In a randomized, double-blind fashion, 35 patients with mild to moderate essential hypertension received placebo run-in medication for 2 weeks, followed by 4 weeks' moxonidine sustained release (1.5 mg o.d.) or placebo. On the first day and 1 and 4 weeks following the start of treatment, blood pressure was measured and CNS effects were assessed using SPV, visual analogue scales and EEG. Results On day 1 there was a significant, but not clinically relevant, reduction in the time-corrected area under the effect curve (AUEC) for SPV in the moxonidine group compared with placebo [difference of 38degrees s(-1); 95% confidence interval (CI) 23, 52]. This difference was no longer significant after one (9degrees s(-1); 95% CI -17, 35) and 4 weeks (6.9degrees s(-1); 95% CI -16, 30). Visual analogue scales for alertness showed similar results. A decrease in EEG alpha- and beta-power and an increase in delta-power were only found on day 1 of moxonidine treatment. The AUEC for systolic/diastolic blood pressure relative to placebo was 23 (95% CI 17, 29)/13 (9, 16) mmHg lower on day 1 and remained reduced by 20 (11, 30)/12 (6, 17) and 15 (6, 25)/9 (3, 15) mmHg after 1 and 4 weeks' moxonidine treatment. Conclusions Four weeks' treatment with an experimental SR formulation resulted in tolerance to CNS effects (equivalence to placebo) while blood pressure-lowering effects remained adequate. The tolerance to CNS effects was already observed after 1 week of treatment.
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