Astronauts experience Space Motion Sickness requiring treatment with an anti-motion sickness medication, scopolamine during space missions. Bioavailability after oral administration of scopolamine is low and variable, and absorption form transdermal patch is slow and prolonged. Intranasal administration achieves faster absorption and higher bioavailability of drugs that are subject to extrahepatic, first pass metabolism after oral dosing. We examined pharmacokinetics of 0.1, 0.2, and 0.4 mg doses of the Investigational New Drug formulation of intranasal scopolamine gel (INSCOP) in 12 healthy subjects using a randomized, double-blind cross-over study design. Subjects received one squirt of 0.1 g of gel containing either 0.1 mg or 0.2 mg/0.1 mL scopolamine or placebo in each nostril. Serial blood samples and total urine voids were collected after dosing and drug concentrations were determined using a modified LC-MS-MS method. Results indicate dose-linear pharmacokinetics of scopolamine with linear increases in Cmax and AUC within the dose range tested. Plasma drug concentrations were significantly lower in females than in males after administration of 0.4 dose. All three doses were well tolerated with no unexpected or serious adverse side effects reported. These results suggest that intranasal scopolamine gel formulation (INSCOP) offers a fast, reliable, and safe alternative for the treatment of motion sickness.

中文翻译：

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鼻内东pol碱凝胶制剂的剂量递增药代动力学。

宇航员在太空飞行期间遇到太空晕车病，需要使用抗晕车药东碱进行治疗。东oral碱口服后的生物利用度低且变化多端，经皮贴剂的吸收缓慢而延长。经口服给药后，经肝外首过代谢的药物经鼻给药可实现更快的吸收和更高的生物利用度。我们使用随机，双盲交叉研究设计，研究了0.1、0.2和0.4毫克剂量的鼻内东pol碱凝胶（INSCOP）的研究用新药制剂的药代动力学，在12名健康受试者中进行了研究。受试者接受一喷0.1 g的凝胶，每个鼻孔中含有0.1 mg或0.2 mg / 0.1 mL的东pol碱或安慰剂。给药后收集系列血样和总尿液空隙，并使用改良的LC-MS-MS方法确定药物浓度。结果表明东pol碱的剂量线性药代动力学在所测试的剂量范围内Cmax和AUC呈线性增加。服用0.4剂后，女性血浆药物浓度显着低于男性。所有三种剂量均耐受良好，没有意外或严重的不良副作用报道。这些结果表明，鼻内东碱凝胶制剂（INSCOP）为晕动病的治疗提供了一种快速，可靠和安全的替代方法。服用0.4剂后，女性血浆药物浓度显着低于男性。所有三种剂量均耐受良好，没有意外或严重的不良副作用报道。这些结果表明，鼻内东碱凝胶制剂（INSCOP）为晕动病的治疗提供了一种快速，可靠和安全的替代方法。服用0.4剂后，女性血浆药物浓度显着低于男性。所有三种剂量均耐受良好，没有意外或严重的不良副作用报道。这些结果表明，鼻内东pol碱凝胶制剂（INSCOP）为晕动病的治疗提供了一种快速，可靠和安全的替代方法。