THE EFFECT OF SBE4-BETA-CD ON IM PREDNISOLONE PHARMACOKINETICS AND TISSUE-DAMAGE IN RABBITS - COMPARISON TO A COSOLVENT SOLUTION AND A WATER-SOLUBLE PRODRUG

The i.m. pharmacokinetics of prednisolone (5 mg/kg) in eight rabbits a fter its administration in a co-solvent (40:10:50; PEG 400/ethanol/wat er) mixture, in a slightly hypertonic 0.09 M SBE4-beta-CD (a sulfobuty l ether derivative variably substituted on the 2-, 3- and the 6-positi ons of beta-cyclodextrin) solution and from a water-soluble prodrug, t he W-phosphate ester, disodium salt were studied. Muscle damage as mea sured by changes in plasma creatine kinase (CK) levels caused by the a dministration of the three solutions was also assessed. The prednisolo ne plasma AUC values over 24 h from the SBE4-beta-CD formulation and t he phosphate eater were 87.0 +/- 12.6 and 78.0 +/- 14.1% of that from co-solvent, respectively. The apparent bioavailability of prednisolone over 24 h from the SBE4-beta-CD formulation and its prodrug was not s ignificantly different from that of the co-solvent. The changes in CK levels from the SBE4-beta-CD were identical to those from normal salin e, however, the co-solvent mixture caused significantly elevated CK le vels. The presence or absence of prednisolone had no affect on the rel ative CK levels for the cyclodextrin solution and the normal saline. T here was a small effect noted for the co-solvent, with and without pre dnisolone. These results confirm that i.m. administered drugs, such as prednisolone, appear to be rapidly, quantitatively and safely release d from SBE4-beta-CD inclusion complexes. SBE4-beta-CD may provide an a lternative to the use of co-colvents and possibly even prodrugs for th e i.m. delivery of sparingly water-soluble drugs such as prednisolone.