Carruthers S G, Shoeman D W, Hignite C E, Azarnoff D L
Clin Pharmacol Ther. 1978 Apr;23(4):375-82. doi: 10.1002/cpt1978234375.
The sedative and antihistamine effects of diphenhydramine were assessed in relation to plasma concentration after placebo, diphenhydramine 50 mg intravenously, and diphenhydramine 50 mg orally to each of 6 healthy volunteers on three separate occasions. Diphenhydramine plasma elimination t1/2 was 3.0 to 4.3 hr, volume of distribution was 188 to 336 L, and clearance was 637 to 1,014 ml/min. Systemic bioavailability of the oral preparation ranged from 0.26 to 0.60. The sedative effect of intravenous diphenhydramine differed from that of placebo only during the first 3 hr. Antihistamine effect, as measured by reduction of histamine provoked skin wheal diameter, was significantly different from that of placebo for at least 8 hr. There was a positive correlation between plasma diphenhydramine level and sedative and antihistamine effects, but wide variation in the extent and rate of change of these effects were observed between the subject. There appears to be a concentration range of 25 to 50 ng/ml, within which there is significant antihistamine effect without significant sedation.
在6名健康志愿者身上，分三次分别给予安慰剂、静脉注射50毫克苯海拉明和口服50毫克苯海拉明，评估苯海拉明的镇静和抗组胺作用与血浆浓度的关系。苯海拉明的血浆消除半衰期为3.0至4.3小时，分布容积为188至336升，清除率为637至1014毫升/分钟。口服制剂的全身生物利用度为0.26至0.60。静脉注射苯海拉明的镇静作用仅在最初3小时内与安慰剂不同。以组胺诱发的皮肤风团直径减小来衡量的抗组胺作用，至少在8小时内与安慰剂有显著差异。血浆苯海拉明水平与镇静和抗组胺作用之间存在正相关，但在受试者之间观察到这些作用的程度和变化速率有很大差异。似乎存在一个25至50纳克/毫升的浓度范围，在此范围内有显著的抗组胺作用而无明显的镇静作用。
