Asunto(s)
Enfermedades de los Caballos , Subtipo H3N8 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Infecciones por Orthomyxoviridae , Caballos , Animales , Humanos , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/veterinaria , Vacunación/veterinaria , Enfermedades de los Caballos/prevención & control , Anticuerpos AntiviralesRESUMEN
OBJECTIVE: To determine the pharmacokinetics of pergolide after IV administration to horses. ANIMALS: 8 healthy adult horses. PROCEDURES: Pergolide mesylate was administered IV at a dose of 20 µg/kg (equivalent to 15.2 µg of pergolide/kg) to each horse, and blood samples were collected over 48 hours. Pergolide concentrations in plasma were determined by means of high-performance liquid chromatography-tandem mass spectrometry, and pharmacokinetic parameters were determined on the basis of noncompartmental methods. RESULTS: After IV administration of pergolide, mean ± SD clearance, elimination half-life, and initial volume of distribution were 959 ± 492 mL/h/kg, 5.64 ± 2.36 hours, and 0.79 ± 0.32 L/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: With an elimination half-life of approximately 6 hours, twice-daily dosing may be more appropriate than once-daily dosing to reduce peak-trough fluctuation in pergolide concentrations. Further pharmacodynamic and pharmacokinetic studies of pergolide and its metabolites will be necessary to determine plasma concentrations that correlate with clinical effectiveness to determine the therapeutic range for the treatment of pituitary pars intermedia dysfunction.
Asunto(s)
Agonistas de Dopamina/farmacocinética , Caballos/metabolismo , Pergolida/farmacocinética , Administración Intravenosa , Animales , Cromatografía Liquida/veterinaria , Agonistas de Dopamina/administración & dosificación , Agonistas de Dopamina/sangre , Masculino , Pergolida/administración & dosificación , Pergolida/sangre , Espectrometría de Masas en Tándem/veterinariaRESUMEN
Pergolide, an ergot-derived dopamine D2 receptor agonist, is used extensively as an orally administered treatment for pituitary pars intermedia dysfunction (PPID) in horses. One of the barriers associated with pergolide determinations in plasma for pharmacokinetic applications has been the technically demanding requirement for sensitivity. The objective of our work was to develop a simple assay for the determination of pergolide in plasma and demonstrate its potential application in the study of pergolide pharmacokinetics (PK) in horses. A UPLC-MS/MS assay was developed with a simple sample preparation involving methanol protein precipitation and injection of supernatant. The assay was applied to samples from a horse dosed with 10mg pergolide (as the mesylate salt) by nasogastric intubation. Plasma samples were collected over a 48h period. The assay demonstrated performance sufficient to enable application to low level PK studies. Within-batch precision and accuracy were within acceptance criteria; precision was less than 10% RSD (n=5) and accuracy was -7.3% at 0.014ng/mL, the lower limit of quantification was 0.006ng/mL and the method detection limit was 0.002ng/mL. In the treated horse, Cmax was 0.40ng/mL and the assay easily allowed determination of plasma levels in the elimination phase to 48h. In conclusion, this assay using UPLC-MS/MS and methanol protein precipitation easily meets the challenging demands of pergolide analyses in plasma.