Matejcek M, Irwin P, Neff G, Abt K, Wehrli W
Int J Clin Pharmacol Ther Toxicol. 1985 May;23(5):258-66.
Ketotifen (Zaditen) is a new, orally active benzocycloheptathiophene derivative for use in the prophylaxis of asthma. Besides possessing anti-allergic properties, it also has H1-receptor mediated antihistaminic activity. Drugs which block H1-receptors are known to have some sedative properties. On the other hand the bronchodilator theophylline is a CNS stimulant. We investigated whether these side-effects could be reduced by concomitant administration. In a balanced-sequence crossover study, 12 healthy males received placebo, 1 mg ketotifen + 300 mg theophylline, 1 mg ketotifen + 600 mg theophylline, and each drug separately at 1-week intervals. Quantified electroencephalograms, cardiovascular and behavioral measurements, symptom reports, and blood drug assays were used to assess the drug interaction. Results showed EEG and behavioral effects with both ketotifen and theophylline alone which were less evident with the drugs in combination. Blood drug levels were not altered by combined drug administration. These findings suggest a mutual attenuation of the CNS effects of ketotifen and theophylline at therapeutic doses and encourage their combined use in asthma therapy. The combined effect may be optimized by modifying formulations or timing. The applicability of quantitative EEG to such problems is well demonstrated.
酮替芬（佐迪泰）是一种新型的口服活性苯并环庚噻吩衍生物，用于预防哮喘。除了具有抗过敏特性外，它还具有H1受体介导的抗组胺活性。已知阻断H1受体的药物具有一定的镇静特性。另一方面，支气管扩张剂茶碱是一种中枢神经系统兴奋剂。我们研究了同时给药是否可以减少这些副作用。在一项平衡序列交叉研究中，12名健康男性每隔1周接受安慰剂、1毫克酮替芬 + 300毫克茶碱、1毫克酮替芬 + 600毫克茶碱，以及每种药物单独给药。通过定量脑电图、心血管和行为测量、症状报告以及血药测定来评估药物相互作用。结果显示，单独使用酮替芬和茶碱时脑电图和行为效应明显，而联合使用时这些效应不太明显。联合给药未改变血药水平。这些发现表明，在治疗剂量下，酮替芬和茶碱对中枢神经系统的作用相互减弱，并鼓励它们在哮喘治疗中联合使用。通过调整剂型或给药时间，联合效应可能会得到优化。定量脑电图在这类问题上的适用性得到了很好的证明。
