Miller Jodi L, Ashford J Wesson, Archer Sanford M, Rudy Anita C, Wermeling Daniel P
Solvay Pharmaceuticals, Inc., Marietta, Georgia, USA.
Pharmacotherapy. 2008 Jul;28(7):875-82. doi: 10.1592/phco.28.7.875.
To evaluate the pharmacokinetics of haloperidol after intranasal administration compared with intravenous and intramuscular administration, and to evaluate systemic and local tolerance of intranasal administration.
Randomized, open-label, three-way crossover study.
Academic medical center.
Four healthy volunteers (two men, two women; aged 24-37 yrs).
Each subject received in a randomized order the following three treatments, with a 2-week washout period between treatments: intravenous haloperidol 2.5 mg (0.5 ml of 5.0 mg/ml) infused over 15 minutes, intramuscular haloperidol 2.5 mg (0.5 ml of 5.0 mg/ml), and intranasal haloperidol 2.5 mg (2.5 mg/0.1-ml spray into a single naris).
Blood samples were obtained serially and plasma levels determined. Noncompartmental analysis was used to estimate pharmacokinetic parameters. Physical and nasal examinations and adverse-effect profiles were obtained to assess tolerance. Mean (percent coefficient of variation) haloperidol bioavailability after intranasal administration was 63.8% (24.4%) compared with intravenous administration and 48.6% (29.4%) compared with intramuscular administration. Intranasal administration achieved higher peak levels that occurred more quickly compared with intramuscular administration. Median time to maximum concentration was 15 minutes after the intranasal dose compared with 37.5 and 15 minutes after the intramuscular and intravenous doses, respectively. Subjects had mild-to-moderate systemic adverse effects, all related to an extension of haloperidol's pharmacologic actions. Two of the four subjects complained of mild-tomoderate nasal irritation after the intranasal doses.
Our results suggest that additional research studies are warranted for further evaluation of intranasal administration of haloperidol. The product provides rapid therapeutic plasma levels and sedation, with only minor and short-lived nasal irritation. These data suggest that intranasal administration of haloperidol, or other antipsychotics with similar potency, could play a role in treating psychiatric emergencies.
评估与静脉注射和肌肉注射相比，鼻内给药后氟哌啶醇的药代动力学，并评估鼻内给药的全身和局部耐受性。
随机、开放标签、三向交叉研究。
学术医疗中心。
四名健康志愿者（两名男性，两名女性；年龄24 - 37岁）。
每位受试者按随机顺序接受以下三种治疗，治疗间隔为2周的洗脱期：静脉注射2.5毫克氟哌啶醇（0.5毫升5.0毫克/毫升），15分钟内输注完毕；肌肉注射2.5毫克氟哌啶醇（0.5毫升5.0毫克/毫升）；鼻内给予2.5毫克氟哌啶醇（2.5毫克/0.1毫升喷雾剂喷入一侧鼻腔）。
连续采集血样并测定血浆水平。采用非房室分析来估算药代动力学参数。进行体格检查和鼻腔检查以及获取不良反应情况以评估耐受性。与静脉注射相比，鼻内给药后氟哌啶醇的平均（变异系数百分比）生物利用度为63.8%（24.4%），与肌肉注射相比为48.6%（29.4%）。与肌肉注射相比，鼻内给药达到的峰值水平更高且出现更快。鼻内给药后达到最大浓度的中位时间为15分钟，而肌肉注射和静脉注射后分别为37.5分钟和15分钟。受试者出现轻度至中度全身不良反应，均与氟哌啶醇药理作用的扩展有关。四名受试者中有两名在鼻内给药后抱怨有轻度至中度的鼻腔刺激。
我们的结果表明，有必要进行更多研究以进一步评估氟哌啶醇的鼻内给药。该产品能快速达到治疗性血浆水平并产生镇静作用，仅伴有轻微且短暂的鼻腔刺激。这些数据表明，鼻内给予氟哌啶醇或其他效力相似的抗精神病药物可能在治疗精神科急症中发挥作用。
