Vanmolkot Floris H M, de Hoon Jan N J M
Center for Clinical Pharmacology, University Hospital Gasthuisberg (K.U. Leuven), Leuven, Belgium.
Br J Clin Pharmacol. 2005 Apr;59(4):387-97. doi: 10.1111/j.1365-2125.2005.02333.x.
To assess the reproducibility of the forearm blood flow (FBF) response to intra-arterial infusion of calcitonin-gene related peptide (CGRP), measured by venous occlusion plethysmography. In addition, to compare different ways of expressing the FBF response and perform sample size calculations.
On two separate visits, CGRP (10 ng min(-1) dl(-1) forearm) was infused for 45 min into the brachial artery of six healthy subjects. Reproducibility was assessed by calculating mean difference, repeatability coefficient, within-subject coefficient of variation (WCV) and intraclass correlation coefficient.
CGRP increased FBF from 2.8 +/- 0.4 and 3.2 +/- 0.7 (at baseline) to 15.4 +/- 1.4 and 15.2 +/- 1.5 ml min(-1) dl(-1) forearm (at 45 min) on visits 1 and 2, respectively (P < 0.0001 for both visits). Mean difference in FBF at 45 min between both visits was 0.3 ml min(-1) dl(-1) forearm (repeatability coefficient: 4.1 ml min(-1) dl(-1) forearm). This FBF response appeared to be more reproducible when expressed as absolute FBF in the infused arm (WCV 11%) compared with absolute FBF-ratio between both arms (WCV 37%), percentage change from baseline in FBF in the infused arm (WCV 29%) and percentage change from baseline in FBF-ratio (WCV 40%). When expressed as absolute FBF, a sample size of five (95% confidence interval: 2-12) subjects gives 90% power at a type I error probability of 0.05 to detect a 25% shift in FBF response.
Intra-arterial infusion of CGRP results in a forearm vasodilator response which is reproducible between days. This response is most reproducible when expressed as absolute FBF. The presented methodology provides a suitable pharmacodynamic model to assess the in vivo activity of CGRP-receptor antagonists in a small number of subjects.
通过静脉阻断体积描记法评估动脉内输注降钙素基因相关肽（CGRP）后前臂血流量（FBF）反应的可重复性。此外，比较表达FBF反应的不同方式并进行样本量计算。
在两次单独的访视中，将CGRP（10 ng·min⁻¹·dl⁻¹前臂）输注到6名健康受试者的肱动脉中45分钟。通过计算平均差异、重复性系数、受试者内变异系数（WCV）和组内相关系数来评估可重复性。
在第1次和第2次访视时，CGRP分别使FBF从2.8±0.4和3.2±0.7（基线时）增加到15.4±1.4和15.2±1.5 ml·min⁻¹·dl⁻¹前臂（45分钟时）（两次访视P均<0.0001）。两次访视45分钟时FBF的平均差异为0.3 ml·min⁻¹·dl⁻¹前臂（重复性系数：4.1 ml·min⁻¹·dl⁻¹前臂）。与双臂间绝对FBF比值（WCV 37%）、输注臂FBF相对于基线的百分比变化（WCV 29%）以及FBF比值相对于基线的百分比变化（WCV 40%）相比，当以输注臂的绝对FBF表示时，这种FBF反应似乎更具可重复性。当以绝对FBF表示时，5名受试者（95%置信区间：2 - 12）的样本量在I型错误概率为0.05时具有90%的检验效能，以检测FBF反应中25%的变化。
动脉内输注CGRP会导致前臂血管舒张反应，且在不同日期之间具有可重复性。当以绝对FBF表示时，这种反应的可重复性最佳。所提出的方法提供了一种合适的药效学模型，可在少数受试者中评估CGRP受体拮抗剂的体内活性。
