DROP SIZE AND INITIAL DOSING FREQUENCY PROBLEMS OF TOPICALLY APPLIED OPHTHALMIC DRUGS
DROP SIZE AND INITIAL DOSING FREQUENCY PROBLEMS OF TOPICALLY APPLIED OPHTHALMIC DRUGS
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DOI：
10.1002/jps.2600630304
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发表时间：
1974-01-01
影响因子：
3.8
通讯作者：
ROBINSON, JR
中科院分区：
文献类型：
--
作者：
CHRAI, SS;MAKOID, MC;ROBINSON, JR
对于一滴局部滴眼液，通过引流造成的药物损失量和速率随着滴注溶液体积的增加而增加。然而，滴注药物后，角膜前泪膜中的药物浓度随着滴注量的增加而升高。短时间间隔多次滴注的优点是可以增加角膜前膜中的药物浓度，但缺点是通过引流会导致大量药物损失，对于强效药物来说，这可能会导致全身毒性。当在未麻醉的白化兔子中使用放射性锝 (99mTc) 作为测试物质时，结果表明，与以较短时间间隔给药的相应滴剂给药方案相比，滴剂之间 5 分钟的间隔可最大限度地减少药物的引流损失和角膜前膜中的药物浓度积聚。随着滴药之间的时间间隔缩短到滴一滴后立即滴另一滴，通过引流损失的药物量和泪膜药物浓度都会增加。两种药物的单独给药在剂量方案方面存在很大的问题。放射性锝稀释和引流研究以及房水药物浓度和瞳孔缩小研究表明，向眼睛添加药物的顺序、滴注溶液的体积以及滴注第一种和第二种药物的时间都会影响每种药物的最终活性。一般来说，施用的第一种药物总是比第二种药物遭受更大的损失，并且损失程度与滴注的每种药物的体积和滴注之间的时间间隔成正比。讨论了本研究对临床实践的影响。无论何时需要多种药物治疗，本报告中提供的多种药物数据都构成了联合药物产品的有力论据。
The amount and rate of drug loss through drainage, for a single drop of topically applied ophthalmic solution, increase with increasing volume of instilled solution. However, the concentration of drug in the precorneal tear film immediately after instillation of drug is higher with larger instilled volumes. Multiple drops administered at short time intervals have the advantage of increasing drug concentration in the precorneal film but the disadvantage of considerable drug loss through drainage, which for potent drugs can lead to systemic toxicity. When using radioactive technetium (99mTc) as the test substance in unanesthetized albino rabbits, it was shown that a 5‐min interval between drops minimizes drainage loss of drug and the drug concentration buildup in the precorneal film as compared to the corresponding dosage regimen of drops administered at shorter time intervals. As the time interval between drops shortens to the point of one drop followed immediately by another drop, both the amount of drug lost through drainage and the tear film concentration of drug increase. Separate administration of two drugs presents a great problem as to dosage regimen. It was shown by radioactive technetium dilution and drainage studies, as well as by aqueous humor drug concentration and miosis studies, that the order of addition of drug to the eye, the volume of solution instilled, and the time of instillation of the first and second drugs all influence the ultimate activity of each drug. In general terms, the first drug administered always suffers a greater loss than the second drug and the degree of loss is proportional to the volume of each drug instilled and the time interval between drops. The implications of the present study to clinical practice are discussed. The multidrug data presented in this report constitute a strong argument for combination drug products whenever multidrug therapy is indicated.