Vogel G, Becker U, Ulbrich M
Arzneimittelforschung. 1975 Jul;25(7):1037-9.
The influence of movements of fluid from the blood into the bowel lumen (solvent drag) on absorption of drugs from the intestine was studied in conscious rats with surgically implanted duodenal tubes. The drugs were given to the rats by intraduodenal instillation either in isotonic saline or in solutions of mannite having twice or three times the osmotic pressure of the blood. The instillation of hypertonic mannite solutions leads to concentration-dependent exsorption of fluid. The drugs tested were atropine and azoniaspiro compound XVII (azoniaspiro[3alpha-benziloyloxy-nortropan-8,1'-pyrrolidine]-chloride), both of which are poorly absorbed, and phenobarbital and nicotine, both of which are well absorbed. The criteria used to assess the rate of entry of the drugs into the blood stream were "efficacy" and "toxicity". In the case of atropine, azoniaspiro compound XVII and nicotine mortality rate and survival time were measured, while in the case of phenobarbital the latent period between instillation of the solution and onset of the hypnotic effect was used. As the tonicity of the solution was raised, so the concentration-dependent "efficacy" and "toxicity" declined. This meant that the latent period after instillation of phenobarbital lengthened, while after instillation of atropine, azoniaspiro compound XVII and nicotine in solutions of increasing tonicity the mortality fell and survival was prolonged. The only exception to this generalization was found when azoniaspiro compound XVII was instilled in triple strength mannite solution. The reasons for this exception were not ascertained. From the results it is concluded that "solvent drag" is an important factor in the absorption of drugs from the intestine. A stream of fluid passing into the lumen interferes with absorption, and this is reflected in the diminished "efficacy" and "toxicity" of the drug. Another factor which may influence the absorption of the drugs tested is the fall in concentration resulting from the inflow of fluid into the bowel lumen. This tends to flatten the concentration gradient between the bowel lumen and the blood and therefore delays absorption.
利用外科植入十二指肠插管的清醒大鼠，研究了血液中液体向肠腔移动（溶剂拖曳）对药物肠道吸收的影响。通过十二指肠内滴注，将药物以等渗盐水或渗透压为血液两倍或三倍的甘露醇溶液给予大鼠。高渗甘露醇溶液的滴注导致液体的浓度依赖性外渗。所测试的药物有阿托品和氮杂螺环化合物XVII（氮杂螺[3α - 苯甲酰氧基 - 降托烷 - 8,1'-吡咯烷] - 氯化物），二者吸收都很差，还有苯巴比妥和尼古丁，二者吸收都很好。用于评估药物进入血流速率的标准是“药效”和“毒性”。对于阿托品、氮杂螺环化合物XVII和尼古丁，测定死亡率和存活时间，而对于苯巴比妥，则使用溶液滴注与催眠效果开始之间的潜伏期。随着溶液张力升高，浓度依赖性的“药效”和“毒性”下降。这意味着苯巴比妥滴注后的潜伏期延长，而在滴注阿托品、氮杂螺环化合物XVII和尼古丁于张力不断增加的溶液中时，死亡率下降且存活时间延长。当在三倍浓度的甘露醇溶液中滴注氮杂螺环化合物XVII时，发现了这一普遍规律的唯一例外情况。该例外情况的原因尚未确定。从结果可以得出结论，“溶剂拖曳”是药物肠道吸收的一个重要因素。进入肠腔的液流会干扰吸收，这反映在药物“药效”和“毒性”的降低上。另一个可能影响所测试药物吸收的因素是液体流入肠腔导致的浓度下降。这往往会使肠腔与血液之间的浓度梯度变平，从而延迟吸收。
