Huang C H, Kimura R, Nassar R B, Hussain A
J Pharm Sci. 1985 Jun;74(6):608-11. doi: 10.1002/jps.2600740605.
The effect of rate of perfusion, volume, pH of the perfusate, and partition coefficient of the drug on the rate of in situ nasal absorption in rats was examined. The studies showed that the rate constant for the nasal absorption of phenobarbital was independent of the rate of perfusion above a value of 2 mL/min. The nasal absorption of benzoic acid was found to depend on the pH of the perfusate with the benzoate anion being absorbed at a rate one-fourth of that of benzoic acid. The effect of lipid solubility on the extent of nasal absorption was studied using a series of barbiturates. The rate and extent of absorption was found to be dependent on the chloroform-water partition coefficient of the barbiturate. The effect of the volume of the perfusate on the absorption rate constant of phenobarbital, phenol red, tyrosine, and propranolol was studied. The data obtained showed that a linear relationship existed between the rate constants of absorption and the reciprocal of the volume of the perfusate. Using this in situ relationship it was possible to predict in vivo absorption rate constants for propranolol and L-tyrosine when volumes of 0.1 mL were administered. The calculated values for these compounds were found to be close to those determined in in vivo experiments. This indicates that the in situ technique can be used to predict in vivo absorption rate constants.
研究了灌注速率、灌注液体积、灌注液pH值及药物分配系数对大鼠鼻腔原位吸收速率的影响。研究表明，当灌注速率高于2 mL/min时，苯巴比妥鼻腔吸收的速率常数与灌注速率无关。发现苯甲酸的鼻腔吸收取决于灌注液的pH值，苯甲酸根阴离子的吸收速率是苯甲酸的四分之一。使用一系列巴比妥类药物研究了脂溶性对鼻腔吸收程度的影响。发现吸收速率和程度取决于巴比妥类药物的氯仿-水分配系数。研究了灌注液体积对苯巴比妥、酚红、酪氨酸和普萘洛尔吸收速率常数的影响。获得的数据表明，吸收速率常数与灌注液体积的倒数之间存在线性关系。利用这种原位关系，可以预测当给药体积为0.1 mL时普萘洛尔和L-酪氨酸的体内吸收速率常数。发现这些化合物的计算值与体内实验测定的值接近。这表明原位技术可用于预测体内吸收速率常数。
