Determination of dexmedetomidine in rat plasma by a sensitive [3H]clonidine radioreceptor assay

Publication Type:

Journal Article

Authors:

Bol, C.J.; AP, I.J.; Danhof, M.; Mandema, J.W.

Source:

J Pharm Sci, Volume 86, Number 7, p.822-6 (1997)

ISBN:

0022-3549 (Print)

DOI Name (links to online publication)

10.1021/js960478u10.1021/js960478u [pii]

Keywords:

Adrenergic alpha-Agonists/*blood/metabolism; Adrenergic alpha-Antagonists/metabolism; Animals; Binding; Competitive; Cattle; Clonidine/*metabolism; Idazoxan/analogs; &; derivatives/metabolism; Imidazoles/*blood/metabolism; Magnesium/pharmacology; Male;

Abstract:

This paper describes the development and implementation of a sensitive radioreceptor assay (RRA) for determining concentrations of dexmedetomidine, an alpha-2 adrenergic agonist with anesthetic properties, in rat plasma. Calf retina membranes were selected as the alpha-2 adrenergic receptor source, and the alpha-2 antagonist [3H]RX821002 and the alpha-2 agonist [3H]clonidine were evaluated as radioligands. We optimized the binding conditions for both radioligands and chose a radioligand for implementation in the RRA based on the characteristics of the inhibition binding curves with dexmedetomidine. The final method is based on competition between the radioligand [3H]clonidine and dexmedetomidine for high-affinity binding sites present in calf retina membranes. The assay has a coefficient of variation of 8% in the range 23.7-592 pg for 0.2 mL of plasma. This assay can be applied to pharmacokinetic-pharmacodynamic studies of dexmedetomidine.