Scintigraphic studies on the corneal residence of a New Ophthalmic Delivery System (NODS): rate of clearance of a soluble marker in relation to duration of pharmacological action of pilocarpine.
1. A gamma scintigraphic study has been carried out on the precorneal residence and pharmacodynamic action of a radiolabelled New Ophthalmic Delivery System (NODS) containing pilocarpine nitrate in 12 healthy volunteers. 2. The NODS was radiolabelled with the soluble marker technetium-99m labelled diethylenetriaminepentaacetic acid, to mark the release characteristics of soluble drugs contained within the matrix. 3. The relationship between the precorneal residence time of the marker and the duration of drug effect on intraocular pressure and pupil diameter was monitored. Results obtained following administration of the NODS were compared with those obtained after administration of a 25 microliters drop of a 2% w/v pilocarpine nitrate solution. Each formulation was administered to one eye only, the other eye acting as a control. 4. Dissolution of the radiolabel from the NODS in vivo showed considerable intersubject variation with half-times of dissolution ranging from 46 s to 833 s (mean +/- s.d. -280 +/- 217 s), the mean (+/- s.d.) half-time of clearance of the radiolabel from the NODS and corneal region of interest was 406 +/- 214 s whereas the radiolabelled solution had a mean (+/- s.d.) ocular surface residence time of 2.9 +/- 1.5 s. 5. Pupil diameter and intraocular pressure were measured for 5 h post-administration of the NODS and the solution. After both treatments pupil diameter was significantly constricted in the test eye when compared with the control eye (P less than 0.001; Student's paired t-test). Pupil diameter was constricted by 52% after administration of the NODS and by 35% after administration of the solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Greaves
J L
JL
Department of Physiology and Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
Wilson
C G
CG
Birmingham
A T
AT
Richardson
M C
MC
Bentley
P H
PH
D000328:Adult; D003315:Cornea / Q000000981:diagnostic imaging / Q000378:metabolism*; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D010862:Pilocarpine / Q000008:administration & dosage* / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D011877:Radionuclide Imaging
D015609:Organotechnetium Compounds; D010862:Pilocarpine