Bondesson Eva, Bengtsson Thomas, Nilsson Lars-Erik, Wollmer Per
AstraZeneca R&D Lund, SE-221 87, Lund, Sweden.
Pharm Res. 2006 Sep;23(9):2122-8. doi: 10.1007/s11095-006-9013-6. Epub 2006 Aug 11.
The effects of a natural surface-active agent, sodium taurocholate (NaTC), on the absorption of a hydrophilic solute, technetium-99m-labelled diethylene triamine pentaacetic acid (99mTc-DTPA), deposited at various sites within the airways were evaluated in this open, cross-over, and single-dose study.
Nine healthy non-smokers received 99mTc-DTPA with or without the addition of NaTC, administered as an oropharyngeal aerosol and as nebulized large and fine droplet-sized pulmonary aerosols delivered by Pari and UltraVent nebulizers inhaled at fairly rapid and slow flows, respectively. Plasma concentration versus time profiles and 24-h urinary excretion of radioactivity were assessed. Further, 99mTc-labelled human serum albumin nanocolloidal particles (99mTc-Nanocoll) were administered with or without NaTC by Pari and followed by repeated chest gamma-imaging.
NaTC changed no pharmacokinetic parameters for oropharyngeal 99mTc-DTPA. Independent of intrapulmonary 99mTc-DTPA deposition pattern, NaTC reduced Tmax (Pari: -0.8 h; UltraVent: -1.5 h) and mean absorption time (MAT) (-0.4 h; -0.7 h), and increased bioavailability (+13%; +44%) and dose-adjusted Cmax (+54%; +103%). NaTC decreased the pulmonary 99mTc-Nanocoll disappearance half-life from 8 h and 45 min to 4 h and 19 min.
Our findings suggest that NaTC increases both rate and extent of 99mTc-DTPA absorption throughout the lower airways, without changing 99mTc-DTPA absorption in the oral cavity.
在这项开放性、交叉、单剂量研究中，评估了一种天然表面活性剂牛磺胆酸钠（NaTC）对沉积于气道内不同部位的亲水性溶质——锝-99m标记的二乙三胺五乙酸（99mTc-DTPA）吸收的影响。
9名健康非吸烟者接受了添加或未添加NaTC的99mTc-DTPA，分别通过口咽气雾剂以及由Pari和UltraVent雾化器递送的大液滴和小液滴尺寸的肺部气雾剂给药，吸入流速分别为较快和较慢。评估了血浆浓度-时间曲线以及24小时放射性尿排泄。此外，通过Pari给予添加或未添加NaTC的99mTc标记的人血清白蛋白纳米胶体颗粒（99mTc-Nanocoll），随后进行重复胸部γ成像。
NaTC未改变口咽99mTc-DTPA的任何药代动力学参数。与肺内99mTc-DTPA沉积模式无关，NaTC缩短了达峰时间（Pari：-0.8小时；UltraVent：-1.5小时）和平均吸收时间（MAT）（-0.4小时；-0.7小时），并提高了生物利用度（+13%；+44%）和剂量校正的Cmax（+54%；+103%）。NaTC使肺部99mTc-Nanocoll消失半衰期从8小时45分钟缩短至4小时19分钟。
我们的研究结果表明，NaTC增加了整个下呼吸道99mTc-DTPA的吸收速率和程度，而不改变口腔中99mTc-DTPA的吸收。
