Tfelt-Hansen P, Paalzow L
Clin Pharmacol Ther. 1985 Jan;37(1):29-35. doi: 10.1038/clpt.1985.7.
Ergotamine tartrate (0.5 mg) was injected intramuscularly into 10 subjects with migraine. The effect on peripheral arteries, measured as a decrease in toe-arm systolic gradients, developed slowly and was well sustained after 29 hr. In contrast, ergotamine was quickly absorbed (t1/2 = 3 min) and plasma levels (measured by HPLC) declined, with a biologic t1/2 of 2.5 hr. A hypothetic effect compartment model was adopted and kinetic and dynamic data were simultaneously fitted on a computer. Calculated from mean data, the rate constant for equilibration of the drug between plasma and effector site was 0.07 hr-1, with a t1/2 of 9.9 hr, and the steady-state plasma concentration resulting in 50% of maximal effect (Cpss50) was 0.24 ng/ml. The largest variability for the estimated kinetic and dynamic parameters among subjects was found for Cpss50 (coefficient of variation = 110%), indicating that, in addition to some kinetic variability, dynamic variability (difference in sensitivity) should be anticipated in the therapeutic use of ergotamine.
将酒石酸麦角胺（0.5毫克）肌肉注射给10名偏头痛患者。以趾-臂收缩压差降低来衡量，其对外周动脉的作用起效缓慢，在29小时后仍维持良好。相比之下，麦角胺吸收迅速（t1/2 = 3分钟），血浆水平（通过高效液相色谱法测定）下降，生物半衰期为2.5小时。采用了一个假设的效应室模型，并在计算机上同时拟合动力学和动态数据。根据平均数据计算，药物在血浆和效应部位之间平衡的速率常数为0.07小时-1，t1/2为9.9小时，产生最大效应50%时的稳态血浆浓度（Cpss50）为0.24纳克/毫升。在各受试者中，估计的动力学和动态参数的最大变异性出现在Cpss50上（变异系数 = 110%），这表明，在麦角胺的治疗应用中，除了一些动力学变异性外，还应预期到动态变异性（敏感性差异）。
