Pergolide mesylate

Pergolide mesylate is an antiparkinsonian agent which functions as a dopaminergic agonist.

Effects of pergolide mesylate on transduction efficiency of PEP-1-catalase protein.[Pubmed:21324306]

Biochem Biophys Res Commun. 2011 Mar 18;406(3):336-40.

The low transduction efficiency of various proteins is an obstacle to their therapeutic application. However, protein transduction domains (PTDs) are well-known for a highly effective tool for exogenous protein delivery to cells. We examined the effects of Pergolide mesylate (PM) on the transduction of PEP-1-catalase into HaCaT human keratinocytes and mice skin and on the anti-inflammatory activity of PEP-1-catatase against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation using Western blot and histological analysis. PM enhanced the time- and dose-dependent transduction of PEP-1-catalase into HaCaT cells without affecting the cellular toxicity. In a mouse edema model, PEP-1-catalase inhibited the increased expressions of inflammatory mediators and cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1beta, and tumor necrosis factor-alpha induced by TPA. On the other hand, PM alone failed to exert any significant anti-inflammatory effects. However, the anti-inflammatory effect of co-treatment with PEP-1-catalase and PM was more potent than that of PEP-1-catalase alone. Our results indicate that PM may enhance the delivery of PTDs fusion therapeutic proteins to target cells and tissues and has potential to increase their therapeutic effects of such drugs against various diseases.

Pharmacokinetic and pharmacodynamic properties of pergolide mesylate following long-term administration to horses with pituitary pars intermedia dysfunction.[Pubmed:27301465]

J Vet Pharmacol Ther. 2017 Apr;40(2):158-164.

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((R)) ) 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.

Multitemperature stability and degradation characteristics of pergolide mesylate oral liquid.[Pubmed:21507864]

J Pharm Pract. 2010 Dec;23(6):570-4.

The stability of Pergolide mesylate in an oral aqueous liquid was studied. Stability and solubility data were used to determine the degradation characteristics of the drug in this formulation. Samples were stored in the dark at 35 degrees C, 45 degrees C, and 60 degrees C. At 1, 2, 4, 8, 12, and 16 weeks, samples were removed and stored in a -80 degrees C freezer for high performance liquid chromatography (HPLC) assay at a later date. The initial drug concentration of 0.30 mg/mL was determined by assay after storage at -80 degrees C. A solubility of 6.9 mg/mL was found for Pergolide mesylate in the oral liquid at room temperature with a relative standard deviation (RSD) of 4.0%. The degradation process is considered first-order at 25 degrees C and 35 degrees C. At higher temperatures (45 degrees C and 60 degrees C), a color change and curvature at the latter time points in degradation profiles are ascribed to the presence of methylcellulose. The activation energy calculated for degradation of Pergolide mesylate in the oral liquid was 21.3 kcal/mol. The time to reach 90% potency (t90) values were calculated to be 43 days and 3 days, respectively, for storage at 25 degrees C and 35 degrees C. Drug concentrations up to ~6 mg/mL can be maintained as a solution at room temperature with this formulation.

Single-dose oral pharmacokinetics of pergolide mesylate in healthy adult mares.[Pubmed:20949429]

Vet Ther. 2010 Spring;11(1):E1-8.

Pituitary pars intermedia dysfunction (PPID) is probably the most common disease of geriatric horses. Affected horses show a variety of clinical signs, including hirsutism, polyuria/polydipsia, immunosuppression, muscle wasting, and laminitis. The most common treatment for PPID is pergolide, a dopamine agonist; however, there are no pharmacokinetic data about the use of this drug in horses. This article describes a study designed to address this complete lack of pharmacokinetic information. The pharmacokinetics of pergolide are described in a small group of relatively young, healthy mares (n = 6), with the objective of generating data on which to base larger studies in the future. To make definitive dosing recommendations to clinicians, more studies will be needed to investigate the relationship between plasma pergolide concentrations and clinical outcomes, as well as the effect of gender, age, and concomitant disease on the absorption and disposition of this drug.