Haaga M, Kaila T, Salminen L, Ylitalo P
Department of Ophthalmology, University of Tampere, Finland.
Pharmacol Toxicol. 1998 Jan;82(1):19-22. doi: 10.1111/j.1600-0773.1998.tb01392.x.
Ocular and systemic absorption and antagonist activity of topical 1% cyclopentolate were studied in 11 elderly patients undergoing extracapsular cataract extraction, and in 8 healthy female volunteers. The patients received two 35 microl drops of cyclopentolate unilaterally and the healthy volunteers one 30 microl drop bilaterally to the lower conjunctival cul-de-sac of the eye. The drug concentrations were measured with radioreceptor assay and receptor occupancies with radiooccupancy assay using isolated rat brain muscarinic cholinoceptors. In the patient group, cyclopentolate concentrations in aqueous humour were approximately 3000 times higher than those in plasma. Muscarinic cholinoceptors were occupied totally (more than 99.9%) by aqueous humour and 3-18% by plasma taken at 55-125 min. after the drug application. In healthy volunteers peak plasma concentration of cyclopentolate, 2.06+/-0.86 (mean+/-S.D.) nM, occurred at 53 min., maximum receptor occupancy being 5.9+/-2.1%. The maximum pupillary dilatation occured at 30 min. after the drug application. At the same time the near point of vision was extended to more than 50 cm in all subjects. After topical application plasma receptor occupancy was not high enough to cause any significant changes in heart rate and in PQ time. None of the subjects experienced subjectively or objectively adverse effects to be attributed to cyclopentolate.
对11例接受白内障囊外摘除术的老年患者和8名健康女性志愿者，研究了局部应用1%环喷托酯的眼内及全身吸收情况和拮抗活性。患者单侧滴入两滴35微升的环喷托酯，健康志愿者双侧各滴入一滴30微升的环喷托酯至眼下部结膜囊。采用放射受体分析法测定药物浓度，并用放射性占据分析法测定使用离体大鼠脑毒蕈碱胆碱能受体时的受体占有率。在患者组，房水中环喷托酯浓度比血浆中约高3000倍。用药后55 - 125分钟采集的房水使毒蕈碱胆碱能受体完全被占据（超过99.9%），血浆使其占据3 - 18%。在健康志愿者中，环喷托酯的血浆峰值浓度为2.06±0.86（均值±标准差）nM，出现在53分钟时，最大受体占有率为5.9±2.1%。用药后30分钟出现最大瞳孔散大。同时所有受试者的近点视力延长至50厘米以上。局部用药后血浆受体占有率不足以引起心率和PQ间期的任何显著变化。所有受试者均未主观或客观地经历可归因于环喷托酯的不良反应。
