Umut S, Gemicioğlu B, Yildirim N, Barlas A, Ozüner Z
Department of Pulmonology, Cerrahpaşa Medical Faculty, Istanbul University, Turkey.
Int J Clin Pharmacol Ther Toxicol. 1992 May;30(5):149-52.
The bronchodilator, respiratory center and respiratory muscle effects of oral sustained release theophylline are investigated with a placebo controlled double-blind study in 34 patients with chronic obstructive lung disease (COLD). The first 3 days were a theophylline washout period and the patients did not receive theophylline and on the 4th day, serum theophylline concentration was negligible. Initial pulmonary function tests were performed. Twenty-four of the patients took 350 mg oral sustained release theophylline twice a day. Ten of the patients were given placebo. On day 7, serum theophylline concentrations of the study group were in therapeutic doses and the tests were repeated. Bronchodilator effect was assessed by spirometry, flow-volume loops and measuring airway resistance (Raw). Respiratory muscle function was assessed by measuring maximal inspiratory (PImax) and expiratory pressures (PEmax) and the effect on respiratory center was evaluated by minute ventilation, mouth occlusion pressure index and inspiratory duty ratio. Forced vital capacity in one second (p less than 0.001), maximal mid expiratory flow rate (p less than 0.05), maximal expiratory flow at 50 percent of vital capacity (p less than 0.001), maximal inspiratory pressure (p less than 0.01) increased, while airway resistance (p less than 0.05) decreased significantly. Mouth occlusion pressure and minute ventilation mouth occlusion pressure index did not change after theophylline therapy. In placebo group, there was no significant change in airway obstruction assessed by spirometry and flow volume loops or in respiratory muscle function assessed by maximal respiratory pressures. It is therefore, concluded that oral sustained release theophylline has a bronchodilator effect in irreversible chronic obstructive lung disease, increases respiratory muscle function, but in therapeutic doses has no effect on respiratory center.
采用安慰剂对照双盲研究，对34例慢性阻塞性肺疾病（COLD）患者口服缓释茶碱的支气管扩张、呼吸中枢及呼吸肌效应进行了研究。前3天为茶碱洗脱期，患者未接受茶碱治疗，第4天血清茶碱浓度可忽略不计。进行了初始肺功能测试。24例患者每天服用两次350mg口服缓释茶碱。10例患者服用安慰剂。第7天，研究组血清茶碱浓度处于治疗剂量，重复进行测试。通过肺活量测定、流量-容积环和测量气道阻力（Raw）评估支气管扩张作用。通过测量最大吸气压力（PImax）和呼气压力（PEmax）评估呼吸肌功能，并通过分钟通气量、口腔闭合压指数和吸气负荷比评估对呼吸中枢的影响。一秒用力肺活量（p<0.001）、最大呼气中期流速（p<0.05）、肺活量50%时的最大呼气流量（p<0.001）、最大吸气压力（p<0.01）增加，而气道阻力（p<0.05）显著降低。茶碱治疗后口腔闭合压和分钟通气口腔闭合压指数未改变。在安慰剂组，通过肺活量测定和流量-容积环评估的气道阻塞或通过最大呼吸压力评估的呼吸肌功能无显著变化。因此，得出结论：口服缓释茶碱对不可逆慢性阻塞性肺疾病有支气管扩张作用，可增加呼吸肌功能，但在治疗剂量下对呼吸中枢无影响。
