[Effects of pre-instilled mydriatics on the intraocular concentration and anti-inflammatory action of topical 0.1% pranoprofen (2)--Study on multiple dosing].
We studied the effects of multiple dosing and pre-instilled mydriatics (0.5% tropicamide and 0.5% phenylephrine) on the intraocular concentration and anti-inflammatory action of topical 0.1% pranoprofen (PPF) in rabbit eyes. PPF was applied in a single or multiple doses: 1 to 4 times consecutively at 5-minute intervals with or without pre-instilled mydriatics. PPF concentrations in the aqueous humor increased dose-dependently. The PPF concentrations also increased dose-dependently, and reached the maximal concentration by instillation 3 times in the presence of pre-instilled mydriatics, and the concentrations were 3.4 to 5.8 times higher than those without mydriatics. The PPF concentrations in the cornea, secondary aqueous, and iris-ciliary body increased in a dose-dependent manner, and the concentrations were higher in the presence of mydriatics. PPF reduced the protein rise in the secondary aqueous and miotic responses which were seen after paracentesis. The percent inhibitions ranged from 75 to 83, but the inhibitory actions were not enhanced by increases of intraocular PPF concentrations. These data indicate that the potent anti-inflammatory actions of PPF were obtainable by a single instillation, but it might be useful to instill the drug 3 times consecutively to ensure higher intraocular drug concentrations in combination with pre-instilled mydriatics.
Ogawa
T
T
Department of Ophthalmology, Jichi Medical School, Tochigi, Japan.
Ohara
K
K
Shimizu
H
H
D000287:Administration, Topical; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000494:pharmacology; D001578:Benzopyrans / Q000493:pharmacokinetics* / Q000494:pharmacology; D005123:Eye / Q000378:metabolism*; D007322:Instillation, Drug; D008297:Male; D009184:Mydriatics / Q000008:administration & dosage / Q000494:pharmacology*; D011422:Propionates / Q000493:pharmacokinetics* / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects; D011817:Rabbits; D014018:Tissue Distribution; D014331:Tropicamide / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D009184:Mydriatics; D011422:Propionates; C043940:pyranoprofen; D014331:Tropicamide