LACRIMAL AND PLASMATIC KINETICS OF MORPHINE AFTER AN OPHTHALMIC DELIVERY OF 3 DIFFERENT FORMULATIONS

The aims of this work were to study the influence of a thermoreversibl e gel and an insert containing morphine on lacrimal and plasmatic kine tics in comparison with a simple solution. Lacrimal uptake was carried out with a Millipore filter which was characterized by a total recove ry of morphine and an absence of interference on the CPG/SM procedure. Contrary to the thermoreversible gel, the inserts prolonged the lacri mal and plasmatic kinetics. In the lacrimal fluid, Cmax was reduced fr om 21.9 to 4.8 mg/ml and Tmax delayed from 2.9 to 51.4 minutes. Likewi se, in the plasma, Cmax was decreased from 116 to 37 ng/ml and Tmax pr olonged from 17 to 135 minutes. This plasmatic prolongation was equiva lent to the one reported with oral prolonged release devices containin g morphine. Moreover, the insert areas under the curve (taking account of the delivered dose) in the lacrimal fluid and in the plasma were m ultiplied by from 1.6 and 2.6, respectively, in comparison with the so lution.