Hydrolysis of prednisolone succinate by esterase in rabbit ocular tissue.
Prednisolone concentrations in serum after both subconjunctival and intravenous injections of prednisolone sodium succinate at a 1 mg/kg equivalent dose of prednisolone in rabbits were analyzed by regularly phased high-performance liquid chromatography. The systemic availability after subconjunctival injection was determined to be almost 1.0 by comparing areas under the serum concentration-time curves for both administration routes. The initial hydrolytic rate of prednisolone succinate ester was dependent on the amount of total protein in ocular tissue homogenates and fluids as well as that in serum. The rate followed Michaelis-Menten kinetics, with an almost consistent Michaelis constant. Although the maximum hydrolytic rate per unit amount of tissue protein was the highest in conjunctival tissue, followed by corneal tissue and serum, the esterase activity corrected by total protein in the whole rabbit body should be the highest in serum, followed by conjunctival tissue. These results indicate that prednisolone sodium succinate administered subconjunctivally is hydrolyzed rapidly by esterase and absorbed almost completely into the systemic circulation.
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
A
A
Tsuji
I
I
Tamai
K
K
Sasaki
D000818:Animals; D003228:Conjunctiva / Q000201:enzymology; D003315:Cornea / Q000201:enzymology; D004950:Esterases / Q000378:metabolism*; D005123:Eye / Q000201:enzymology*; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D011817:Rabbits
D011239:Prednisolone; D004950:Esterases; C021322:prednisolone hemisuccinate