Nanoparticle methadone: pharmacokinetics and antinociceptive effects in horses

• Grant number: 11/00892-3
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date until: May 01, 2011
• End date until: November 30, 2013
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Clinics and Surgery
• Principal Investigator: Stelio Pacca Loureiro Luna
• Grantee: Nadia Crosignani Outeda
• Host Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated research grant: 10/08967-0 - Evaluation of clinical and experimental pain in animals, AP.TEM

Abstract

The prevention and treatment of pain in animals is very important as pain produces several undesirable effects. Studies to develop improved techniques for pain management deserve attention. Methadone besides being a ¼ agonist, is a antagonist of N-methyl D-aspartate receptor (NMDA) and inhibits norepinephrine reuptake, which could contribute to a more efficient analgesia. Nanoparticles of biodegradable polymers can provide vectorization of a sustained and controlled acting as carriers of drugs, which increases efficacy and reduces adverse events (Sukhorukov et al., 2005). The use of opioids in horses for treatment of pain is limited, due to the short half life when administered intravenously, as well as by side effects. A formulation with a smaller dose of methadone, but with an optimized therapeutic effect, could potentially reduce the cost, with fewer adverse effects such as increased locomotor activity, CNS excitement, sympathetic activation and intestinal hypomotility. The hypothesis of this study is that nanocoated methadone promotes analgesia with lower doses of the drug and therefore with less risk of adverse effects, combined to a more prolonged effect. In this context, this study aims to develop a long-term formulation methadone for clinical use in horses, assessing its analgesic effect and pharmacokinetic profile. The suspensions of nanocapsules will be prepared by interfacial deposition of preformed polymers for further study of sterilization and stability. Six adult horses will receive 0.4 mg/kg of free or nanocoated methadone IV or orally. Pharmacokinetic studies will be undertaken in samples of serum and cerebrospinal fluid by non-compartmental and compartmental analysis, high performance liquid chromatography. The pharmacodynamic study will be performed by investigating the thermal and electrical nociceptive stimulation, as well as intestinal motility scores, correlating with the pharmacokinetic profile. A patent for the new formulation will be applied. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CROSIGNANI, N.; LUNA, S. P.; DALLA COSTA, T.; PIMENTA, E. L.; DETONI, C. B.; GUTERRES, S. S.; PUOLI FILHO, J. N.; PANTOJA, J. C.; PIGATTO, M. C.. Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses. JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS, v. 40, n. 4, p. 398-405, AUG 2017. (11/00892-3, 10/08967-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

OUTEDA, Nadia Crosignani. Estudo farmacocinético e farmacodinâmico de cloridrato metadona por via oral, intramuscular e intravenosa e carreadores lipídicos nanoparticulados de metadona via oral em equinos. 2013. Doctoral Thesis - Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu Botucatu.