Géraud Gilles, Keywood Charlotte, Senard Jean Michel
Service de Neurologie, CHU Rangueil, 1 Avenue Jean Poulhès, 31054 Toulouse, France.
Headache. 2003 Apr;43(4):376-88. doi: 10.1046/j.1526-4610.2003.03073.x.
Triptan use is associated with headache recurrence, and this has been cited as an important reason for patient dissatisfaction with the treatment. The mechanism by which recurrence occurs is not clear, and the incidence of recurrence varies with the triptan used. In order to explore the pharmacological and physiological interaction of triptans and migraine headache recurrence further, some specific clinical, pharmacological, and pharmacokinetic factors that might influence migraine recurrence were evaluated in a review of the major efficacy data for the drugs in the triptan class. These factors were 5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life of each triptan, and the clinical efficacy of each compound, determined by the proportion of patients with headache relief and the therapeutic gain over placebo.
Clinical data were derived from 31 triptan, placebo-controlled, major efficacy studies used in a previous meta-analysis. The mean recurrence rate, mean headache response, and therapeutic gain were calculated using the results from the individual clinical studies. Mean headache response and therapeutic gain were calculated at the time point used to define recurrence in each study. Data for binding affinity and potency were taken from a direct-comparison in vitro pharmacology study, and the elimination half-life quoted in the data sheet for each triptan was used. Rank correlation with recurrence rate was performed for each of the test parameters.
Mean headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for rizatriptan. Elimination half-life and recurrence were inversely correlated (r = -1.0, P =.0016). There was also a significant inverse correlation between 5-HT1B receptor potency and recurrence (r = -0.68, P =.034), but 5-HT1D receptor potency was not correlated with recurrence (r = -0.20, P =.54). In addition, the binding affinities for the 5-HT1B and 5-HT1D receptors were not correlated to headache recurrence. Importantly, it also was demonstrated that initial clinical efficacy was not correlated to headache recurrence. The correlation coefficient for headache response was 0.18 (P =.53) and for therapeutic gain, -0.11 (P =.71).
The incidence of migraine headache recurrence varies between drugs in the triptan class. Migraine recurrence does not appear to be related to initial clinical efficacy, but is influenced by the pharmacological and pharmacokinetic properties of the individual triptans. The triptans with longer half-lives and greater 5-HT1B receptor potency had the lowest rates of headache recurrence.
使用曲坦类药物与头痛复发有关，这被认为是患者对治疗不满的一个重要原因。复发发生的机制尚不清楚，且复发率因所用曲坦类药物而异。为了进一步探究曲坦类药物与偏头痛复发之间的药理和生理相互作用，在回顾曲坦类药物主要疗效数据时，评估了一些可能影响偏头痛复发的特定临床、药理和药代动力学因素。这些因素包括5-HT1B和5-HT1D受体活性、每种曲坦类药物的药代动力学消除半衰期，以及每种化合物的临床疗效，临床疗效由头痛缓解患者的比例和相对于安慰剂的治疗获益来确定。
临床数据来自先前一项荟萃分析中使用的31项曲坦类药物、安慰剂对照的主要疗效研究。使用各个临床研究的结果计算平均复发率、平均头痛反应和治疗获益。在每个研究中用于定义复发的时间点计算平均头痛反应和治疗获益。结合亲和力和效价的数据取自一项直接比较的体外药理学研究，并使用每种曲坦类药物的数据表中引用的消除半衰期。对每个测试参数进行与复发率的等级相关性分析。
平均头痛复发率范围为，2.5毫克夫罗曲坦为17%，利扎曲坦为40%。消除半衰期与复发呈负相关（r = -1.0，P = 0.0016）。5-HT1B受体效价与复发之间也存在显著负相关（r = -0.68，P = 0.034），但5-HT1D受体效价与复发无相关性（r = -0.20，P = 0.54）。此外，5-HT1B和5-HT1D受体的结合亲和力与头痛复发无关。重要的是，还证明了初始临床疗效与头痛复发无关。头痛反应的相关系数为0.18（P = 0.53），治疗获益的相关系数为-0.11（P = 0.71）。
曲坦类药物中不同药物的偏头痛头痛复发率有所不同。偏头痛复发似乎与初始临床疗效无关，但受各个曲坦类药物的药理和药代动力学特性影响。半衰期较长且5-HT1B受体效价较高的曲坦类药物头痛复发率最低。
