Vlachakis N D, Velasquez M, Alexander N, Maronde R F
Clin Pharmacol Ther. 1983 Dec;34(6):764-9. doi: 10.1038/clpt.1983.247.
We measured the first dosage effect and the long-term effect of lofexidine on blood pressure, heart rate, plasma catecholamines, and their major metabolites in 16 patients with primary hypertension who were receiving 50 mg hydrochlorothiazide twice a day while they were recumbent and upright and during isometric handgrip contraction. We also measured the first dosage effect of lofexidine on forearm blood flow and its long-term effect on plasma renin activity. Lofexidine, both in a single dose and after long-term therapy, induced a substantial fall in blood pressure of patients in recumbent and upright positions, whereas it decreased heart rate in both positions only during long-term dosing. Lofexidine did not prevent or diminish the pressure and heart rate rise by isometric handgrip contractions. Single and long-term lofexidine dosing induced a fall in plasma levels of catecholamines and their metabolites. There was a positive correlation between the fall in blood pressures and the reduction in plasma norepinephrine during long-term therapy. There was a positive correlation between the decrease in blood pressure induced by single doses and by long-term dosing, which suggests that lofexidine in a single dosage at the start of therapy may facilitate identification of responders.
我们在16例原发性高血压患者中测量了洛非西定对血压、心率、血浆儿茶酚胺及其主要代谢产物的首次剂量效应和长期效应，这些患者每天两次服用50 mg氢氯噻嗪，测量时分别处于卧位、立位以及进行等长握力收缩期间。我们还测量了洛非西定对前臂血流量的首次剂量效应及其对血浆肾素活性的长期效应。单剂量及长期治疗后的洛非西定均使卧位和立位患者的血压大幅下降，而仅在长期给药期间两个体位的心率均降低。洛非西定不能预防或减轻等长握力收缩引起的血压和心率升高。单剂量及长期服用洛非西定都能使血浆儿茶酚胺及其代谢产物水平下降。长期治疗期间血压下降与血浆去甲肾上腺素减少之间存在正相关。单剂量和长期给药引起的血压下降之间存在正相关，这表明治疗开始时给予单剂量洛非西定可能有助于识别反应者。
