Diphenhydramine kinetics following intravenous, oral, and sublingual dimenhydrinate administration

Eight healthy volunteers received 50 mg of dimenhydrinate, a theoclate salt of diphenhydramine, orally, sublingually, and intravenously on three separate occasions in random sequence. Plasma diphenhydramine concentrations during 12 h after each dose were measured by gas-liquid chromatography with nitrogen-phosphorous detection. Mean peak plasma concentrations after sublingual administration were slightly lower than after oral dosage (38.3 vs 47.8 ng ml-1), and the time of peak concentration was similar (2.6 vs 2.3 h after dose). These differences did not reach statistical significance. The mean total area under the plasma concentration-time curve (AUC) for sublingual administration was slightly but not significantly smaller than after oral dosage (221 vs 270 h ng ml-1). Systemic availability of diphenhydramine after sublingual dimenhydrinate, measured by the ratio of oral AUC to intravenous AUC, was slightly less than after oral dimenhydrinate (0.58 vs 0.69, NS), and both were significantly less than 1.0. Thus sublingual and oral administration of dimenhydrinate result in comparable, but incomplete, systemic availability of diphenhydramine.     

几种中西药抗人实验模拟运动病效果观察

目的 :选用中药“治晕灵”的主要成分生姜、明天麻等六味草药煎成汤剂、或半量汤剂配西药脑益嗪、山莨菪碱各1 4临床常用量配成复方中西药制剂 ,与目前常用抗晕药晕海宁等中、西药的药效进行比较 ,看中药制剂或中西药复方制剂是否具有较好的抗运动病效果。方法 :选 7名敏感被试者 (女性 ,19～ 2 1岁 ) ,用旋转刺激诱发运动病至出现恶心。按拉丁方设计 ,与安慰剂 (淀粉 10 0mg)及晕海宁 (5 0mg)进行对比 ,分别观察了生姜合剂 (30ml)、晕可平 (30ml)、山莨菪碱 (10mg)、脑益嗪 (2 5mg)及上述复方中西药制剂口服后的运动病耐力。结果 :与安慰剂比较 ,晕海宁、山莨菪碱、脑益嗪、晕可平、生姜合剂、复方中西药制剂分别使运动病耐力提高 5 .4%、7.5 %、5 .9%、7.4%、32 .3 %、2 0 .4% ;生姜合剂效果较优 ,除口服时有辛辣味外 ,无明显的副作用。复方中西药制剂各成分未显示协同作用 ,而只是简单的作用相加。结论 :生姜合剂具有较好的抗运动病作用     

茶苯海明片溶出度的实验研究

本实验参照美国药典21版规定标准考察了国产八批茶苯海明片的溶出度,对其溶出参数T_(?)、T_(?)值进行了方差分析,经实验认为T_(50)、T_d值与崩解时限间具有高度相关性(P<0.01),同时对国内同类产品的溶出度提出了参考标准。     

茶苯海明口腔崩解片及其普通片在恒河猴体内的药代动力学比较

目的：比较茶苯海明口腔崩解片及其普通片在恒河猴体内的药代动力学特征。方法：采用随机、自身对照方法考察两制剂在恒河猴体内的药代动力学特点;采用HPLC-UV法测定分别口服给予相应剂量的药物（均为茶苯海明50 mg）后恒河猴体内血药浓度;并采用DAS2.0对药代动力学参数进行统计分析。结果：茶苯海明口腔崩解片相对生物利用度（F0-12h,F0-∞）分别为（154±42）%和（150±53）%。两制剂间的血药浓度时间-曲线下面积（AUC0-∞）差异无统计学意义（P〉0.05）,而Cmax和AUC0-12差异有统计学意义（P〈0.05）。此外,茶苯海明口腔崩解片tmax与普通片比较明显缩短,但差异无统计学意义（P〉0.05）。茶苯海明在恒河猴空白血浆中10～2000 ng/mL浓度范围内线性良好（r=0.99995）,最低检测限（LLOQ）10 ng/mL。其他确证数据如准确度、精密度等均在要求范围内。结论：茶苯海明口腔崩解片在体内吸收比普通片快。     

Comparison of ondansetron, dimenhydrinate versus placebo as PONV prophylaxis for outpatient gynecological laparoscopy

This is a study comparing ondansetron, dimenhydrinate versus placebo as PONV prophylaxis for outpatient gynecologic laparascopy. Postoperative nausea and vomiting (PONV) is very common following ambulatory gynecological laparoscopy. Prophylactic antiemetic therapy if safe, effective and affordable may reduce the incidence of PONV, expedite hospital discharge and improve patient satisfaction. After institutional review board approval, informed written consent was obtained form 87 ASA I–II women undergoing ambulatory gynecological laparoscopy. In a random and double blind fashion the women were divided into three groups receiving either ondansetron 8 mg, dimenhydrinate 50 mg or placebo. A standard anesthetic technique with propofol, fentanyl, mivacurium, nitrous oxide and isoflurane was used. Measurements of nausea, emesis, pain, drowsiness, and satisfaction and recovery milestones were recorded. Psychomotor recovery was evaluated using p deletion and digit symbol substitution (DSS) test. There was no difference in the groups with respect to demographic data. Dimenhydrinate prolonged immediate recovery and impaired psychomotor recovery, but there was no difference in postanesthesia care unit (PACU) or hospital discharge. The incidence of PONV was minimal. The visual analogue score (VAS) for nausea was only 1 on a scale from 0–10 cm in all groups. Only one patient in the placebo group experienced PACU emesis. The incidence and severity of PONV was so low, even in the placebo group that the use of prophylactic antiemetic therapy cannot be justified.     

Assessment of the rewarding effects of dimenhydrinate using the conditioned place preference paradigm in mice

Dimenhydrinate (DIM) is an over-the-counter antihistamine consisting of diphenhydramine (DIP) and 8-chlorotheophylline (CTP). Medical use of DIM is for prevention of nausea and motion sickness. Recently, it has been reported that DIM may be used alone or in combination with other drugs for recreational purposes due to its euphoric and hallucinogenic effects. To investigate the putatively rewarding properties of DIM and its constituents DIP and CTP, we used a conditioned place preference (CPP) test in mice. DIM significantly induced CPP at a dose of 30 mg/kg. Neither DIP (3, 10, and 30 mg/kg) nor CTP (3, 10, and 30 mg/kg) alone induced CPP. Because neither DIP nor CTP resulted in CPP, the rewarding property of DIM appears to be caused by the sum of the effects of its constituents. In addition, low doses of DIM (3 mg/kg), co-administered with low doses of cocaine (7.5 mg/kg), significantly induced CPP, while neither low-dose DIM (3 mg/kg) nor low-dose cocaine (7.5 mg/kg) administered separately induced CPP. This result suggests the liability of DIM use in combination with other abused drugs to create a stronger effect.     

茶苯海明缓释胶囊的制备与体外释放研究

本中心研制的茶苯海明缓释胶囊采用速释微丸和缓释微丸混合装囊制备而成，比国外品种易于混合均匀，即保持了速释部分，又保持了持久的稳定特性，体外释放曲线在ｐＨ６ ．８、Ｈ２Ｏ及人工胃液中与ＨＯＲＮＥＲ公司产品一致。     

A case-control study of congenital abnormality and dimenhydrinate usage during pregnancy

Objective The objective was to determine the teratogenicity of dimenhydrinate, an anti-emetic drug.Methods We compared patients with congenital abnormalities with matched normal controls. Cases were taken from the population-based data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities between 1980 and 1996, while matched controls were from the National Birth Registry of the Central Statistical Office.Results Out of 38,151 newborn infants with no congenital abnormalities (control group), 1,726 (4.5%) were treated with dimenhydrinate during pregnancy, while out of 22,843 cases with congenital abnormalities, the number was 914 (4.0%; unadjusted prevalence odds ratio with 95% confidence interval: 0.9, 0.8–1.0). There was thus no indication of teratogenicity with dimenhydrinate. However, a lower rate of obstructive uropathy was found in infants born to mothers treated with dimenhydrinate during the first trimester of pregnancy than in infants whose mothers did not take the drug at that time.     

The spiral after effect (SAE) as a measure of motion sickness susceptibility and the effect on the SAE of an antimotion sickness drug and a central nervous system depressant

A study was carried out to determine whether the spiral after effect (SAE) could be considered a reliable measure of motion sickness susceptibility as measured by Reason's motion sickness questionnaire (MSQ). In an initial correlative study it was found that MSQ scores were significantly correlated with neuroticism (N) scores on the Eysenck Personality Inventory. However, the correlation between MSQ and a measure of the SAE duration was not significant. In the subsequent controlled drug study it was shown that both dimenhydrinate, an antinauseant, and temazepam, a minor tranquillizer, decreased the duration of the SAE: although significance was only obtained with the latter drug. The results of both experiments are discussed in terms of Reason's theory of motion sickness and it is suggested, on the basis of Reason's results and those obtained in the present study, that the SAE has both a cortical and a vestibular component in its mechanism of action.     

光纤药物溶出原位过程监测仪评价茶苯海明片的体外溶出度

目的:使用光纤药物溶出原位过程监测仪实时监测不同厂家及批号的茶苯海明片的体外溶出度,以评价其工艺质量。方法:监测仪设置条件为测定波长278nm、基准校正波长550nm,光纤探头规格为2mm,温度37℃,转速50r·min-1,数据采集间隔时间30s,介质为水900mL;采用桨法测定各样品溶出度,并与《中国药典》法比较。结果:监测仪测定结果表明,茶苯海明片所有样品溶出度均符合《中国药典》的相关规定,但溶出曲线不同,即溶出过程存在差异;同一批号的样品采用监测仪及药典法测定虽然45min时的溶出度结果比较无显著性差异,但溶出曲线有差异。结论:与《中国药典》法比较,光纤药物溶出实时监测仪可准确连续地反映药物的溶出过程,获得的数据更加完整、真实,可用于评价产品的体外溶出过程。