Determination of pergolide in horse plasma by UPLC–MS/MS for pharmacokinetic applications

Jacobson, GA; Pirie, Adam; Edwards, Scott; Hughes, Kristopher; Rendle, David; Davies, Noel W.

doi:10.1016/j.jpba.2014.01.016

Cited by 8 publications

(16 citation statements)

References 6 publications

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“…Using a sensitive drug detection assay, all of the horses in both the Jacobson et al . () and Rendle et al . () studies had measurable drug concentrations at 48 h, the last point of sample collection, whereas in the Gehring et al .…”

Section: Discussionmentioning

confidence: 94%

“…This study was designed to answer specific, clinically relevant questions regarding the pharmacokinetic and pharmacodynamic properties after oral pergolide mesylate administration to horses. Recent studies exploring the pharmacokinetic properties of pergolide in younger, healthy animals have resulted in discordant findings, suggesting a need for further investigation (Gehring et al ., ; Jacobson et al ., ; Rendle et al ., ). In the current study, we chose to examine pergolide disposition in nonfasted, aged horses with PPID, using clinically relevant doses and allowing for ample treatment time to ensure the drug had reached steady state and that the drug had time to reach its full effect.…”

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

“…Although several studies have reported the ability of pergolide to control clinical signs and improve diagnostic test results in horses with PPID, limited information is available regarding the pharmacokinetic and pharmacodynamic properties of the drug in the target population (Donaldson et al, 2002;Perkins et al, 2002;Schott, 2004;FDA FOI UCM280354). The few pharmacokinetic studies that have been performed to date have been conducted in healthy, young adult horses following a single dose of pergolide mesylate, whereas in clinical practice, the primary use is longterm administration in aged horses with PPID (Gehring et al, 2010;Jacobson et al, 2014;Rendle et al, 2015). Thus, much remains unknown regarding the use of pergolide in the equine PPID patient.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long‐term administration to horses with pituitary pars intermedia dysfunction

McFarlane

Banse

Knych

et al. 2016

Vet Pharm & Therapeutics

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The objective of this study was to gain an understanding of the pharmacokinetic and pharmacodynamic properties of pergolide in horses with PPID after of long-term oral administration. Six horses with confirmed PPID were treated with pergolide (Prascend ) at 1 mg/horse po q24 h for 2 months, followed by 2 mg/horse po q24 h for 4 months. Following the last dose, plasma samples were collected for measurement of pergolide using an LC/MS/MS method and ACTH measurement using a chemiluminescent immunoassay. Noncompartmental and compartmental pharmacokinetic analyses were performed, as well as pharmacodynamic assessment of the effect of plasma pergolide concentrations on plasma ACTH concentrations. Pergolide effectively decreased plasma ACTH concentration in aged horses with PPID, with similar pharmacokinetic properties as reported in young horses, including an approximate terminal half-life of 24 h. Plasma ACTH concentration increased by 50% in 3/6 horses at 2 days and 6/6 horses 10 days after discontinuing drug administration. Pergolide was quantified in all horses at 2 days and in none at 10 days after last dose. In summary, after discontinuing pergolide treatment, plasma ACTH concentration increased while pergolide was still quantifiable in some horses. Once-daily dosing of pergolide is likely appropriate in most horses with PPID for regulating the plasma ACTH concentration.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long‐term administration to horses with pituitary pars intermedia dysfunction

McFarlane

Banse

Knych

et al. 2016

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

show abstract

“…The first moment curves (AUMC) were calculated by the linear trapezoidal rule, and mean residence time (MRT) was calculated as AUMC/AUC. The ratio of the apparent total body clearance ( Cl / F ) was calculated as dose/AUC 0–∞ (Jacobson et al ., ). The apparent volume of distribution ( V z / F ) was calculated as Cl / K e .…”

Section: Methodsmentioning

confidence: 99%

A sensitive LC‐MS/MS method for quantifying capsaicin and dihydrocapsaicin in rabbit plasma and tissue: application to a pharmacokinetic study

Wang

Meng²,

et al. 2014

Biomedical Chromatography

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Prescription and nonprescription products for topical management of pain, including cream, lotion and patch forms, contain capsaicin (CAP) and dihydrocapsaicin (DHC). There are few in vivo studies on absorption, bioavailability and disposition of CAP and DHC. We established a sensitive and rapid LC-MS/MS assay to determine CAP and DHC levels in rabbit plasma and tissue. Bio-samples prepared by liquid-liquid extraction using n-hexane-dichloromethane-isopropanol (100: 50: 5, v/v/v) mixture were separated by isocratic chromatography with an Extend C18 column. The mobile phase was acetonitrile-water-formic acid (70: 30: 0.1, v/v/v). The method was linear from 0.125 to 50 ng/mL for a 100 μL bio-sample, and the lower quantification limit was 0.125 ng/mL. Total run time to analyze each sample was 3.5 min. We used this validated method to study pharmacokinetics and tissue distribution of CAP gel administered topically to rabbits. A very small amount of CAP and DHC was absorbed into the systemic circulation. The highest plasma concentration was 2.39 ng/mL, and the mean peak plasma concentration value after 12 h of CAP gel application was 1.68 ng/mL. Drug concentration in treated skin was relatively high, with low concentration in other tissues. Thus, topical CAP gel had strong local effects and weaker systemic effects.

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A sub-pathway based method to identify candidate drugs for glioblastomas

2014

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Glioblastomas (GBM) are the most common primary malignant brain tumors with a high invasiveness and resistance to radiation and other treatments. The need for the development of new therapeutic agents for GBM is urgent. Here, we aimed to explore the metabolic mechanism of GBM and identified potential novel drugs for GBM by a sub-pathway-based method. By using the GBM microarray data from "The Cancer Genome Atlas" database, we first identified the 274 differentially expressed genes between GBM and normal samples. Then, we identified 18 significant enriched metabolic sub-pathways that may involve in the development of GBM. Finally, by an integrated analysis of GBM-involved sub-pathways and drug-affected sub-pathways, we identified 66 novel small-molecular drugs capable to target the GBM-involved sub-pathways. Our method could not only identify existing drug (paclitaxel) for GBM, but also predict potentially novel agents (pergolide) that might have therapeutic effects. We also experimentally verified that pergolide could induce GBM cell death. These candidate small-molecular drugs identified by our approach may provide insights into a novel therapy approach for GBM.

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Determination of pergolide in horse plasma by UPLC–MS/MS for pharmacokinetic applications

Cited by 8 publications

References 6 publications

Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long‐term administration to horses with pituitary pars intermedia dysfunction

Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long‐term administration to horses with pituitary pars intermedia dysfunction

A sensitive LC‐MS/MS method for quantifying capsaicin and dihydrocapsaicin in rabbit plasma and tissue: application to a pharmacokinetic study

A sub-pathway based method to identify candidate drugs for glioblastomas

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