A method using a liquid chromatographic-electrospray-mass spectrometric assay for the determination of antimigraine compounds: preliminary pharmacokinetics of MDL 74,721, sumatriptan and naratriptan, in rabbit.
MDL 74,721 (I), sumatriptan(II) and naratriptan(III) are new 5-HT1-like agonists that have potential as a novel treatment for migraine. Liquid chromatographic-electrospray-mass spectrometric (LC-ESI-MS) assay have been developed to compare the pharmacokinetics of these three antimigraine compounds. The concentration of each parent drug was determined using a solid-phase extraction method and LC-ESI-MS analysis demonstrating the high sensitivity and specificity of the methods down to subnanogram levels in rabbit plasma samples. Pharmacokinetic parameters evaluated after administration of single intravenous and oral doses were very similar and the ANOVA analysis did not show any statistically significant differences for t1/2, Cmax, V or AUC (normalised). The pharmacokinetic parameters showed short t1/2 (range 1.14-1.9 h) either after intravenous (i.v.) or oral (p.o.) administration and high total body clearance (CL) after the p.o. dose both probably due to extensive and rapid metabolism of the parent drugs as suggested by the low values for bioavailability (range 13.4-22.8%).
Duléry
B D
BD
Department of Pharmacokinetics, Marion Merrell Research Centre, Strasbourg, France.
Petty
M A
MA
Schoun
J
J
David
M
M
Huebert
N D
ND
D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid; D007211:Indoles / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008297:Male; D013058:Mass Spectrometry; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D013449:Sulfonamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D018170:Sumatriptan / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D014363:Tryptamines; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*
D007211:Indoles; C107347:MDL 74721; D010880:Piperidines; D017366:Serotonin Receptor Agonists; D013449:Sulfonamides; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; D014662:Vasoconstrictor Agents; D018170:Sumatriptan; C106783:naratriptan