Greene Spencer C, Noonan Patrick K, Sanabria Carlos, Peacock W Frank
Department of Emergency Medicine, Ben Taub Hospital, Baylor College of Medicine , Houston, Texas.
PK Noonan Pharmaceutical Consulting, LLC , Williamsburg, Virginia.
Curr Ther Res Clin Exp. 2016 Jun 27;83:1-7. doi: 10.1016/j.curtheres.2016.06.001. eCollection 2016.
Oral solution N-acetylcysteine (NAC) is an antidote for acetaminophen overdose, but its unpleasant taste and aroma can impede delivery even after the coadministration of antiemetic medications. Flavored effervescent NAC tablets dissolved in water might be a more palatable formulation than oral solution NAC diluted with soft drink.
To evaluate the relative bioavailability of these 2 formulations and assess subjective preferences between them.
Thirty healthy adult volunteers (mean [SD] = 35.2 [9.14] years) were enrolled in this open-label, randomized, single-dose, crossover study, with a 7-day washout period. Volunteers were randomized to receive 11 g effervescent test formulation or the reference product under fasting conditions, after which 19 serial blood samples were collected over 48 hours. Total plasma NAC concentrations were evaluated by LC-MS, and pharmacokinetic parameters were calculated. The 2 formulations were considered bioequivalent if the 90% CIs of log-transformed ratios of pharmacokinetic parameters were within the predetermined bioequivalence range (80%-125%) established by the US Food and Drug Administration. Within 15 minutes of dosing, subjects were also asked to rank formulation attributes on a 5-point hedonic scale, with mean group differences analyzed by Wilcoxon signed rank test. Safety-profile assessment included treatment-emergent adverse events, physical examination, chemistry, and hematology parameters.
The concentration-versus-time profiles were similar for the 2 formulations, with mean Cmax of 26.5 μg/mL for effervescent NAC tablets and 28.4 μg/mL for oral solution NAC. The 90% CIs for the pharmacokinetic parameters met the criteria for concluding bioequivalence, and subjects preferred effervescent NAC tablets in terms of taste (P = 0.0247), flavor (P = 0.0082), texture (P = 0.009), and overall likeability (P = 0.0012), but there was no difference for smell (P = 0.0533). All treatment-emergent adverse events were mild, with no differences between the treatment groups.
Data from this study of a single dose of 11 g oral NAC demonstrated that effervescent NAC tablets and oral solution NAC met the regulatory criteria for bioequivalence in fasting healthy adult subjects. Effervescent NAC tablets appear to be a more palatable alternative for treatment of acetaminophen overdose. ClinicalTrials.gov identifier: NCT02723669. (Curr Ther Res Clin Exp. 2016; 83C:1-7) © 2016 Elsevier HS Journals, Inc.
口服溶液N - 乙酰半胱氨酸（NAC）是对乙酰氨基酚过量的解毒剂，但其令人不快的味道和气味即使在同时服用止吐药物后也可能妨碍给药。溶解于水中的调味泡腾NAC片可能比用软饮料稀释的口服溶液NAC更可口。
评估这两种制剂的相对生物利用度，并评估它们之间的主观偏好。
30名健康成年志愿者（平均[标准差]= 35.2 [9.14]岁）参加了这项开放标签、随机、单剂量、交叉研究，洗脱期为7天。志愿者被随机分配在禁食条件下接受11 g泡腾试验制剂或参比产品，之后在48小时内采集19份系列血样。通过液相色谱 - 质谱法评估血浆总NAC浓度，并计算药代动力学参数。如果药代动力学参数对数转换比值的90%置信区间在美国食品药品监督管理局确定的预定生物等效性范围（80% - 125%）内，则认为这两种制剂具有生物等效性。给药后15分钟内，还要求受试者按照5分享乐量表对制剂属性进行排名，通过Wilcoxon符号秩检验分析组间平均差异。安全性评估包括治疗期间出现的不良事件、体格检查、化学和血液学参数。
两种制剂的浓度 - 时间曲线相似，泡腾NAC片的平均Cmax为26.5μg/mL，口服溶液NAC为28.4μg/mL。药代动力学参数的90%置信区间符合生物等效性判定标准，受试者在味道（P = 0.0247）、风味（P = 0.0082）、质地（P = 0.009）和总体喜好度（P = 0.0012）方面更喜欢泡腾NAC片，但在气味方面无差异（P = 0.0533）。所有治疗期间出现的不良事件均为轻度，治疗组之间无差异。
这项单剂量11 g口服NAC研究的数据表明，泡腾NAC片和口服溶液NAC在禁食的健康成年受试者中符合生物等效性的监管标准。泡腾NAC片似乎是治疗对乙酰氨基酚过量更可口的替代选择。ClinicalTrials.gov标识符：NCT02723669。（《当前治疗研究与临床实验》。2016年；83C：1 - 7）©2016爱思唯尔HS期刊公司
