A new specific enzyme immunoassay allowing an efficient pharmacokinetic evaluation of gamma-cyclodextrin after intravenous administration to rats

Purpose. Because of its ability to form complexes with drugs, gamma-cyclode xtrin is of great potential value in pharmaceutical formulations. The biolo gical fate of gamma-cyclodextrin must therefore be considered in safety eva luation, using sensitive and specific methods applicable to biological flui ds. Methods. Antibodies were raised against gamma-cyclodextrin, allowing the de velopment of a new enzyme immunoassay. The analytical characteristics of th is assay were evaluated. Rats were given a single intravenous 25 mg/kg dose of gamma-cyclodextrin. Plasma and urine samples were collected and assayed . Results. This new enzyme immunoassay was sensitive (limit of detection clos e to 94 pg/mL) and suitable for quantification of gamma-cyclodextrin in uri ne and plasma after methanol extraction. The use of different linear and cy clic compounds demonstrated the high specificity of the assay. After i.v. a dministration, the concentration of gamma-cyclodextrin rapidly decreased in the plasma while the molecule was probably distributed into the tissues. A lthough urinary elimination predominates, only 50% of the injected gamma-cy clodextrin was recovered in urine, suggesting enzymatic degradation and/or tissular storage. Conclusions. This assay may provide important information on the fate of ga mma-cyclodextrin inclusion complexes dedicated to drug-delivery using vario us modes of administration (oral, parenteral, transmucosal or dermal).