Effects of pretreatment with mydriatics on intraocular penetration of 0.1% pranoprofen.
The mechanism by which an increase in the intraocular concentration of topically applied 0.1% pranoprofen (PPF) is induced by pretreatment with Mydrin P (0.5% tropicamide and 0.5% phenylephrine) was studied in rabbit eyes. In separate experiments, solutions of each of the various ingredients contained in Mydrin P ophthalmic solution were applied 60 minutes prior to instillation of PPF. Ninety minutes after PPF instillation, its concentration in the cornea, aqueous humor and iris-ciliary body were measured by high performance liquid chromatography. PPF concentration was not increased by pretreatment with benzalkonium chloride, chlorobutanol or tropicamide, but was increased by pretreatment with phenylephrine (PHE). After the latter, the PPF concentration was 2 to 3 times higher than that obtained without Mydrin P. It is noteworthy that the concentration of PHE in the aqueous humor also was found to be increased about 3 times in the presence of PPF. The lipophilicity of PPF, judged by the octanol/buffer partition coefficient, was increased when mixed with PHE. These findings indicate that the increase in intraocular PPF concentration after pretreatment with Mydrin P was caused by PHE. This may be attributable to the enhancement of corneal permeability to PPF resulting from formation of an ion-pair complex between the anionic PPF and the cationic PHE.
Ogawa
T
T
Department of Ophthalmology, Jichi Medical School, Tochigi, Japan.
Ohara
K
K
Shimizu
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D001578:Benzopyrans / Q000493:pharmacokinetics*; D002463:Cell Membrane Permeability; D005123:Eye / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D009883:Ophthalmic Solutions; D010656:Phenylephrine / Q000627:therapeutic use; D011292:Premedication; D011422:Propionates / Q000493:pharmacokinetics*; D011817:Rabbits; D014331:Tropicamide / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D009883:Ophthalmic Solutions; D011422:Propionates; D010656:Phenylephrine; C043940:pyranoprofen; D014331:Tropicamide