Immunoassays for the detection of nicergoline and its metabolites in human plasma.
In order to determine nicergoline pharmacokinetics after oral administration to humans, we have developed two radioimmunoassays, one directed against nicergoline and the other directed against known nicergoline metabolites. The assays were validated according to the recommendations of international regulatory agencies and their limits of quantification were 40 and 10 pg/ml, respectively. In order to further validate the methods, a chromatographic separation of immunoreactive entities was performed with samples from healthy volunteers who were given 15 mg of Sermion (nicergoline orally administered). Chromatographic determination of assay specificity showed that the metabolite radioimmunoassay recognised known nicergoline metabolites but also a new metabolite. Using the antibodies directed against nicergoline, we were unable to detect nicergoline in the human plasma. This suggests that nicergoline is absent in the circulation because of complete metabolism through its first-pass effect.
CEA, Service de Pharmacologie et d'Immunologie, DSM/DRM CEA/Saclay, 91191 Gif-sur-Yvette, France. ezan@dsvidf.cea.fr
E
E
Ezan
L
L
Delestre
S
S
Legendre
R
R
Rivière
J L
JL
Doignon
J M
JM
Grognet
D000317:Adrenergic alpha-Antagonists / Q000097:blood* / Q000378:metabolism; D000328:Adult; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D008297:Male; D009530:Nicergoline / Q000097:blood* / Q000378:metabolism; D010865:Pilot Projects; D015203:Reproducibility of Results
D000317:Adrenergic alpha-Antagonists; D009530:Nicergoline