SYSTEMIC AND OCULAR ABSORPTION AND ANTAGONIST ACTIVITY OF TOPICALLY APPLIED CYCLOPENTOLATE IN MAN

Ocular and systemic absorption and antagonist activity of topical 1 % cyclopentolate were studied in 11 elderly patients undergoing extracap sular cataract extraction, and in 8 healthy female volunteers. The pat ients recieved two 35 mu l drops of cyclopentolate unilaterally and th e healthy volunteers one 30 mu l drop bilaterally to the lower conjunc tival cul-de-sac of the eye. The drug concentrations were measured wit h radioreceptor assay and receptor occupancies with radiooccupancy ass ay using isolated rat brain muscarinic cholinoceptors. In the patient group, cyclopentolate concentrations in aqueous humour were approximat ely 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 vo lunteers peak plasma concentration of cyclopentolate, 2.06+/-0.86 (mea n+/-S.D.) nM, occurred at 53 min., maximum receptor occypancy being 5. 91+/-2.1%. The maximum pupillary dilatation occured at 30 min. after t he drug application. Al the same time the near point of vision was ext ended to more than 50 cm in all subjects. After topical application pl asma receptor occupancy was not high enough to cause any significant c hanges in heart rate and in PQ time. None of the subjects experienced subjectively or objectively adverse effects to be attributed to cyclop entolate.