Walters K M, Mason W D, Badr M Z
University of Missouri-Kansas City 64108.
Drug Metab Dispos. 1993 Mar-Apr;21(2):305-8.
Dimenhydrinate (Dramamine) is the 8-chlorotheophylline salt of diphenhydramine. Dramamine is commercially available as a solution containing 50 mg dimenhydrinate per ml in 50% propylene glycol/5% benzyl alcohol. Studies in which New Zealand albino female rabbits received dimenhydrinate, i.v. and/or im, revealed evidence of inhibition of drug clearance apparently due to exposure to vehicle. Following im administration of 8-chlorotheophylline to naive rabbits, peak drug levels of 420 ng/ml were attained in 60 min which declined exponentially to near baseline levels within 7 hr. Animals treated with an additional im dose 2 days later achieved blood drug levels of > 2000 ng/ml which were sustained for the duration of the experimental period. Initial i.v. administration of 8-chlorotheophylline resulted in peak concentration of about 5000 ng/ml which declined to near baseline levels within 90 min, while 8-chlorotheophylline (i.v.) blood levels in rabbits exposed to im vehicle (2 days prior) appeared to plateau around 250 ng/ml after 60 min. Acute, short-term exposure to im vehicle did not appear to elicit the altered elimination profiles. An investigation of the influence of the recommended vehicle on the bioavailability and clearance of dimenhydrinate in isolated rabbit liver microsomes revealed that vehicle at concentrations > 0.68 mg/ml significantly decreased the percent of drug metabolized. This effect was directly proportional to the concentration of vehicle added. Studies showed this effect to be due to the propylene glycol component of the vehicle.
茶苯海明（晕海宁）是苯海拉明的8 - 氯茶碱盐。晕海宁在市面上以一种溶液形式出售，该溶液每毫升含有50毫克茶苯海明，溶剂为50%丙二醇/5%苯甲醇。在新西兰白化雌性兔静脉内和/或肌内注射茶苯海明的研究中，发现有证据表明药物清除受到抑制，这显然是由于接触了溶剂。给未接触过药物的兔子肌内注射8 - 氯茶碱后，60分钟内达到了420纳克/毫升的药物峰值水平，7小时内呈指数下降至接近基线水平。两天后再给这些动物肌内注射一剂，血液药物水平超过2000纳克/毫升，并在实验期间持续保持。最初静脉注射8 - 氯茶碱导致峰值浓度约为5000纳克/毫升，90分钟内降至接近基线水平，而在（提前两天）接触过肌内注射溶剂的兔子中，静脉注射8 - 氯茶碱60分钟后的血液水平似乎在250纳克/毫升左右趋于平稳。急性短期接触肌内注射溶剂似乎并未引发消除曲线的改变。一项关于推荐溶剂对离体兔肝微粒体中茶苯海明生物利用度和清除率影响的研究表明，浓度>0.68毫克/毫升的溶剂显著降低了药物代谢的百分比。这种效应与添加的溶剂浓度成正比。研究表明这种效应是由于溶剂中的丙二醇成分。
