Abstract
The i.m. pharmacokinetics of prednisolone (5 mg/kg) in eight rabbits after its administration in a co-solvent (40:10:50; PEG 400/ethanol/water) mixture, in a slightly hypertonic 0.09 M SBE4-β-CD (a sulfobutyl ether derivative variably substituted on the 2-, 3- and the 6-positions of β-cyclodextrin) solution and from a water-soluble prodrug, the 21-phosphate ester, disodium salt were studied. Muscle damage as measured by changes in plasma creatine kinase (CK) levels caused by the administration of the three solutions was also assessed. The prednisolone plasma AUC values over 24 h from the SBE4-β-CD formulation and the phosphate ester 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-β-CD formulation and its prodrug was not significantly different from that of the co-solvent. The changes in CK levels from the SBE4-β-CD were identical to those from normal saline, however, the co-solvent mixture caused significantly elevated CK levels. The presence or absence of prednisolone had no effect on the relative CK levels for the cyclodextrin solution and the normal saline. There was a small effect noted for the co-solvent, with and without prednisolone. These results confirm that i.m. administered drugs, such as prednisolone, appear to be rapidly, quantitatively and safely released from SBE4-β-CD inclusion complexes. SBE4-β-CD may provide an alternative to the use of co-colvents and possibly even prodrugs for the i.m. delivery of sparingly water-soluble drugs such as prednisolone.
Published Version
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