A new specific enzyme immunoassay allowing an efficient pharmacokinetic evaluation of gamma-cyclodextrin after intravenous administration to rats.
OBJECTIVE
Because of its ability to form complexes with drugs, gamma-cyclodextrin is of great potential value in pharmaceutical formulations. The biological fate of y-cyclodextrin must therefore be considered in safety evaluation, using sensitive and specific methods applicable to biological fluids.


METHODS
Antibodies were raised against gamma-cyclodextrin, allowing the development of a new enzyme immunoassay. The analytical characteristics of this 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 close to 94 pg/mL) and suitable for quantification of gamma-cyclodextrin in urine and plasma after methanol extraction. The use of different linear and cyclic compounds demonstrated the high specificity of the assay. After i.v. administration, the concentration of gamma-cyclodextrin rapidly decreased in the plasma while the molecule was probably distributed into the tissues. Although urinary elimination predominates, only 50% of the injected gamma-cyclodextrin was recovered in urine, suggesting enzymatic degradation and/or tissular storage.


CONCLUSIONS
This assay may provide important information on the fate of gamma-cyclodextrin inclusion complexes dedicated to drug-delivery using various modes of administration (oral, parenteral, transmucosal or dermal).
Créminon
C
C
CEA, DRM, Service de Pharmacologie et d'Immunologie, CEA-Saclay, Gif s/Yvette, France. creminon@dsvidf2.cea.fr
Djedaïni-Pilard
F
F
Vienet
R
R
Péan
C
C
Grognet
J M
JM
Grassi
J
J
Perly
B
B
Pradelles
P
P
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D001826:Body Fluids; D003429:Cross Reactions; D003505:Cyclodextrins / Q000276:immunology / Q000493:pharmacokinetics* / Q000652:urine; D016503:Drug Delivery Systems; D007124:Immunoenzyme Techniques / Q000379:methods*; D007275:Injections, Intravenous; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D047391:alpha-Cyclodextrins; D047408:gamma-Cyclodextrins
D000906:Antibodies; D003505:Cyclodextrins; D047391:alpha-Cyclodextrins; D047408:gamma-Cyclodextrins; D000110:Acetylcholinesterase; C023792:gamma-cyclodextrin; C032613:alpha-cyclodextrin