Braga P C, Piatti G, Grasselli G, Casali W, Beghi G, Allegra L
Centre of Respiratory Pharmacology, University of Milan, Italy.
Drugs Exp Clin Res. 1992;18(3):105-11.
In bronchopulmonary infections antibiotics can be combined with other drugs, called mucoactive drugs, that act to reduce the abnormal viscoelasticity of the mucus enabling a deeper penetration of more antibiotic into the mucus. Seaprose is a protease that interacts with the polymeric fibrillar structure of the bronchial mucus to shorten the long chains of mucoproteins, DNA and other macromolecules, thus reducing the viscosity of the mucus. In order to assess whether the combination of seaprose (60 mg/8 h) plus erythromycin (500 mg/8 h) allows higher antibiotic levels in sputum than erythromycin (500 mg/8 h) plus placebo, the pharmacokinetic behaviour in sputum and in blood of these two treatments was investigated in a double-blind study in two groups of twenty patients each with bronchopulmonary infections. Serum and sputum levels were determined for each patient at the first and seventh day of the two drug regimens. Statistically significant differences for peak, AUC and MRT, were observed for erythromycin between the first and last dose in the group of patients treated with seaprose plus erythromycin; moreover significant differences for these parameters were observed between the two groups. These findings indicate the presence of a pharmacokinetic synergism between seaprose and erythromycin which allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages.
在支气管肺部感染中,抗生素可与其他药物(称为黏液活性药物)联合使用,这些药物的作用是降低黏液异常的黏弹性,使更多抗生素能更深入地渗透到黏液中。海普瑞酶是一种蛋白酶,它与支气管黏液的聚合纤维结构相互作用,缩短黏蛋白、DNA和其他大分子的长链,从而降低黏液的黏度。为了评估海普瑞酶(60毫克/8小时)加红霉素(500毫克/8小时)联合使用是否比红霉素(500毫克/8小时)加安慰剂能使痰液中的抗生素水平更高,在一项双盲研究中,对两组各20例支气管肺部感染患者进行了这两种治疗方案在痰液和血液中的药代动力学行为研究。在两种药物治疗方案的第一天和第七天,测定了每位患者的血清和痰液水平。在接受海普瑞酶加红霉素治疗的患者组中,观察到红霉素在首剂和末剂之间的峰浓度、曲线下面积和平均滞留时间有统计学显著差异;此外,两组之间在这些参数上也观察到显著差异。这些发现表明海普瑞酶和红霉素之间存在药代动力学协同作用,这使得红霉素能够更轻松、更大量地渗透到支气管分泌物中,发挥杀菌作用并具有治疗优势。