Usharani Pingali, Naidu Maddireddi U R, Reddy B S Parthasarathy, Reddy Mohan
Department of Clinical Pharmacology and Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.
Hetero Drugs Ltd., Hyderabad, India.
Curr Ther Res Clin Exp. 2007 Nov;68(6):400-8. doi: 10.1016/j.curtheres.2007.12.004.
Rupatadine is a histamine receptor type 1 antagonist that has been used to treat allergic rhinitis and urticaria.
The aim of this study was to compare the effect of 2 rupatadine tablet formulations on the inhibition of histamine-induced wheal-and-flare cutaneous responses.
In this single-blind, single oral dose, crossover study, healthy male volunteers were randomized to receive 10 mg of either a rupatadine reference or test formulation after an overnight fast. After a 10-day washout period, the subjects were crossed over to receive the other formulation. Subjects were asked to sit with their arm resting on the table while histamine was injected intradermally. The skin prick test was performed on the upper half of the volunteers' forearms before administration and at 1, 2, 4, 6, 12, and 24 hours after study drug administration. Fifteen minutes after each skin prick test, the wheal-and-flare responses were visualized under a bright lamp. AUC0-24 was the primary end point.The 90% CI of least squares mean ratio (%) of the test: reference formulations for maximum inhibition of histamine-induced wheal-and-flare response (Imax%), Tmax, AUC0-24 mm(2)/h, and AUC0-24%/hr were expected to be within 80% to 125% of untransformed data and 80% to 120% of log-transformed data for the 2 formulations to be considered pharmacodynamically equivalent. Subjects were monitored for any spontaneously reported adverse event (AE) throughout the study. In addition, they were specifically asked about the occurrence of any AEs on a checklist (ie, drowsiness, dizziness, dryness of mouth, itching sensation, headache, nausea) throughout the study.
Of the 15 subjects assessed for inclusion, 12 healthy male volunteers (mean [SD] age, 30 [5] years; height, 162 [6] cm; weight, 58 [6] kg) participated in the study. Administration of reference and test formulations of rupatadine significantly inhibited the histamine-induced cutaneous responses in all subjects (P <0.001). Wheal Imax% with the reference and test formulations was 67.97% (11.57%) and 66.76% (9.40%), respectively. Flare Imax% was 59.06% (11.95%) and 56.92% (16.31%), respectively. None of the subjects withdrew from the study due to AEs. Both formulations were well tolerated except for an itching sensation on injection of histamine in all patients; no subject complained of any adverse drug reaction.
In this small study of healthy adult males, the test formulation of the rupatadine tablet was found to be pharmacodynamically equivalent to the reference formulation, as measured by inhibition of histamine-induced cutaneous wheal-and-flare responses.
卢帕他定是一种组胺1型受体拮抗剂，已用于治疗过敏性鼻炎和荨麻疹。
本研究旨在比较两种卢帕他定片剂剂型对组胺诱导的风团和潮红皮肤反应的抑制效果。
在这项单盲、单次口服剂量、交叉研究中，健康男性志愿者在禁食过夜后随机接受10 mg卢帕他定参比制剂或受试制剂。经过10天的洗脱期后，受试者交叉接受另一种制剂。受试者被要求将手臂放在桌子上坐着，同时进行组胺皮内注射。在给药前以及研究药物给药后1、2、4、6、12和24小时，在志愿者前臂的上半部分进行皮肤点刺试验。每次皮肤点刺试验后15分钟，在明亮灯光下观察风团和潮红反应。AUC0-24是主要终点。对于两种制剂，若要被认为在药效学上等效，则受试制剂与参比制剂的最大组胺诱导风团和潮红反应抑制率（Imax%）、达峰时间（Tmax）、AUC0-24 mm(2)/h以及AUC0-24%/hr的最小二乘均值比（%）的90%置信区间预计应在未转换数据的80%至125%以及对数转换数据的80%至120%范围内。在整个研究过程中，对受试者监测任何自发报告的不良事件（AE）。此外，在整个研究过程中，还专门在一份清单上询问他们是否出现任何不良事件（即嗜睡、头晕、口干、瘙痒感、头痛、恶心）。
在评估纳入的15名受试者中，12名健康男性志愿者（平均[标准差]年龄，30[5]岁；身高，162[6]cm；体重，58[6]kg）参与了研究。卢帕他定参比制剂和受试制剂的给药均显著抑制了所有受试者中组胺诱导的皮肤反应（P<0.001）。参比制剂和受试制剂的风团Imax%分别为67.97%（11.57%）和66.76%（9.40%）。潮红Imax%分别为59.06%（11.95%）和56.92%（16.31%）。没有受试者因不良事件退出研究。除了所有患者注射组胺时出现瘙痒感外，两种制剂的耐受性均良好；没有受试者抱怨任何药物不良反应。
在这项针对健康成年男性的小型研究中，通过抑制组胺诱导的皮肤风团和潮红反应测定，发现卢帕他定片的受试制剂在药效学上与参比制剂等效。
