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[各种降钙素喷雾剂制剂的鼻内吸收]

[Intranasal absorption of various calcitonin spray preparations].

作者信息

Pisati P, Feletti F, De Bernardi M, Tripodi A S, Contos S, Germogli R, Molteni R, Covini D

机构信息

Università di Pavia. Istituto di Farmacologia II.

出版信息

Boll Chim Farm. 1992 Mar;131(3):120-7.

PMID:1418891
Abstract

In a cross-over study performed on 10 patients the intranasal absorption of calcitonin contained in three formulation spray was evaluated. One of them contained biliary acid (sodium taurocholate) as the absorption promoting factor while the other two drugs did not. The dosage of calcitonin in blood was effected by means of radioimmunoassay using salmon calcitonin marked with I126 in competition to the one present in the sample for a limited quantity of specific antibodies for salmon calcitonin. The minimum measurable quantity of calcitonin is 10 pg and the response is linear including values between 20% and 80%. It is observed that the plasmatic concentration of calcitonin dosed in different times after administration of the drug containing sodium taurocholate are always significantly higher (Student "t" test for unpaired data, p less than 0.005) than the measurements after administration of the other two drugs. They are about 8 times higher at the first half an hour, about 6 times after an hour and again double at the second hour. The AUC calculated for sodium taurocholate containing drug (1629 pg/ml/h) results significantly higher in relation to the other two drugs (1133 and 926 pg/ml/h) indicating a better bio-availability of calcitonin contained in that spray. The relative bioavailability between calcitonin spray with sodium taurocholate and the other two drugs in reference resulted to 144% and 176%. The presence of a transmucosal absorption promoting factor at the level of a nasal mucosa, represented in this case by sodium taurocholate, enhances significantly the absorption and the bioavailability of calcitonin present in the formulation spray.

摘要

在一项针对10名患者进行的交叉研究中,评估了三种制剂喷雾中降钙素的鼻内吸收情况。其中一种含有胆汁酸(牛磺胆酸钠)作为吸收促进因子,而另外两种药物则没有。通过放射免疫分析法测定血液中的降钙素剂量,该方法使用用I126标记的鲑鱼降钙素与样品中存在的降钙素竞争有限量的鲑鱼降钙素特异性抗体。降钙素的最小可测量量为10 pg,响应呈线性,范围在20%至80%之间。观察到,在给予含牛磺胆酸钠的药物后不同时间给予的降钙素血浆浓度总是显著高于(未配对数据的学生“t”检验,p小于0.005)给予其他两种药物后的测量值。在前半小时约高8倍,一小时后约高6倍,第二小时再次翻倍。含牛磺胆酸钠药物的计算AUC(1629 pg/ml/h)相对于其他两种药物(1133和926 pg/ml/h)显著更高,表明该喷雾中降钙素的生物利用度更好。含牛磺胆酸钠的降钙素喷雾与其他两种参比药物之间的相对生物利用度分别为144%和176%。在鼻粘膜水平存在的跨粘膜吸收促进因子,在这种情况下由牛磺胆酸钠代表,显著提高了制剂喷雾中降钙素的吸收和生物利用度。

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