title: Pharmacodynamics of a new ophthalmic mydriatic insert in healthy volunteers: potential alternative as drug delivery system prior to cataract surgery.
abstract: Cataract surgery requires a satisfactory degree of mydriasis throughout the entire operation. A phase I, open-labelled, randomised, cross-over trial was conducted in 18 healthy volunteers to compare mydriasis obtained with subsequent administration of phenylephrine 10% and tropicamide 0.5% eyedrops or a new insoluble-matrix retropalpebral ophthalmic insert containing 5.38 mg phenylephrine and 0.28 mg tropicamide. Phenylephrine serum concentrations were measured over 6 hr following each treatment administration. Secondary end-points included cardiovascular, general and local tolerance and quantification of bacterial colonisation of the conjunctiva and the cultured insert, respectively. When normalized to the pupil diameter after conventional treatment, the diameter achieved with the insert was 1.13 (95% confidence interval, 0.94-1.48, P=0.38). Moreover, standard eye drops provided faster effective mydriasis than the insert, starting 30 min. as compared to 90 min. upon treatment administration (P<0.01, repeated-measures ANOVA). Phenylephrine concentrations remained almost undetectable for both treatments and no change in heart rate or blood pressure were observed throughout the study. Only three superficial punctuate keratitis were diagnosed with the insert and two with the eye drops. No significant bacterial contamination of conjunctiva swab and cultured insert was observed. The new insoluble-matrix retropalpebral ophthalmic mydriatic insert produced similar but delayed effective and prolonged mydriasis as compared to the standard delivery system. In addition to its potential usefulness in patients undergoing cataract surgery, such new ophthalmic delivery system may be an advantage in children who need to undergo fundus photography due to the single administration and excellent tolerance as well.
authors.affiliation: Unit of Thepapeutic Research, Lariboisière Hospital, Paris, France. stephane.mouly@lrb.ap-hop-paris.fr
authors.forename: Stéphane
authors.initials: S
authors.lastname: Mouly
authors.forename: Isabelle
authors.initials: I
authors.lastname: Mahé
authors.forename: Belkacem
authors.initials: B
authors.lastname: Haouchine
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Sanson-le-Pors
authors.forename: Patrick
authors.initials: P
authors.lastname: Blain
authors.forename: Yves
authors.initials: Y
authors.lastname: Tillet
authors.forename: Jean
authors.initials: J
authors.lastname: Dewailly
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Mongold
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bergmann
mesh_terms: D000293:Adolescent; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D002387:Cataract Extraction / Q000379:methods*; D003228:Conjunctiva / Q000382:microbiology; D003710:Demography; D003971:Diastole / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D004361:Drug Tolerance; D023381:Endpoint Determination; D005260:Female; D006262:Health; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009184:Mydriatics / Q000008:administration & dosage* / Q000494:pharmacology*; D010656:Phenylephrine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D011680:Pupil / Q000502:physiology; D013599:Systole / Q000187:drug effects; D014331:Tropicamide / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D009184:Mydriatics; D010656:Phenylephrine; D014331:Tropicamide