Clinical pharmacokinetics of the eye. Proctor lecture.
Clinical pharmacokinetics of the eye. Proctor lecture.
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DOI：
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发表时间：
1981-10
影响因子：
4.4
通讯作者：
S. Mishima
中科院分区：
文献类型：
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作者：
S. Mishima
本文综述了眼内滴注药物的药代动力学。讨论了药物在结膜盲囊中的行为，并估计了各种载体的损失率。眼内药物渗透的动力学在人和兔眼中遵循相同的模式。根据兔实验结果，计算了各种药代动力学系数，包括角膜上皮的渗透性。同时，利用已发表的人眼房水中的数据，计算了某些药物在人眼中的角膜渗透性、表观吸收和消除速率常数。从角膜的麻醉反应，表面麻醉剂的表观消除速率常数获得。瞳孔响应被转换成与生物相药物浓度成比例的响应参数。其变化的时间过程符合眼内药物渗透的动力学，并计算了各种药物的表观吸收和消除速率常数。随着眼部色素沉着的增加，后一个常数变得更小。使用相对生物利用度概念可以比较各种载体之间的药物吸收效率。还获得了睫状肌麻痹反应的药代动力学系数。分析了眼内压反应，并建议将流出压、流出阻力和房水形成率的降低率用于剂量反应研究。定义了效应消失率，并给出了三种β-肾上腺素能阻滞剂的结果。
Pharmacokinetics of instilled drugs in the human eye is reviewed. The behavior of drugs in the conjunctival cul-de-sac is discussed, and the loss rates with various vehicles are estimated. Kinetics of intraocular drug penetration follows the same pattern in human and rabbit eyes. From results of rabbit experiments, various pharmacokinetic coefficients are computed, including the permeability of the corneal epithelium. Also, with use of published data in human aqueous, the corneal permeability, apparent absorption, and elimination rate constants are calculated for some drugs in the human eye. From the anesthetic response of the cornea the apparent elimination rate constants of the surface anesthetics are obtained. The pupil response is converted to a response parameter proportional to the biophase drug concentration. The time course of its changes conforms with the kinetics of intraocular drug penetration, and the apparent absorption and elimination rate constants are computed for various drugs. The latter constant becomes smaller with increased ocular pigmentation. Use of the relative bioavailability concept permits comparison of drug absorption efficiency among various vehicles. Pharmacokinetic coefficients are also obtained for the cycloplegic responses. The intraocular pressure response is analyzed, and it is suggested that the reduction ratio in the outflow pressure, outflow resistance, and the aqueous formation rate be used for dose-response studies. The rate of effect disappearance is defined and is given for three beta-adrenergic blocking agents.