Contenção química e perfil farmacocinético da dextrocetamina, isolada em associação ao midazolam em jacaré-tinga Caiman crocodilus Linnaeus (1758) (Crocodylia: Alligatoridade)

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2015-02-27

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Universidade Federal de Goiás

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The purpose of this study was to evaluate the sedative effects, changes in physiological parameters and pharmacokinetic profile of dextro-ketamine alone or in association with midazolam, administered intravenously (cranially or caudally) or by intracoelomic route in Caiman crocodilus. Eight young specimens of spectacled caiman were anesthetized with 10 mg/kg of dextro-ketamine injected through the occipital venous sinus (DO group) or through intracoelomic injection (DI group). In addition, the same dose of dextro-ketamine was associated with 0.5 mg/kg of midazolam and administrated via the same routes (DMI or DMO groups, respectively), or within the caudal venous sinus (DMC group). Prior to drug administration (t0) and during the period of evaluation, heart rate (HR), electrocardiogram, respiratory rate (RR), body temperature (T), righting reflex, muscular relaxation of tail, limbs and head, palpebral and corneal reflexes and response to nociceptive stimuli were evaluated. Light sedation, beginning and end of deep sedation and recovery times were registered. Moreover, 24 hours before the injection of anesthetics and 15, 30, 60, 120, 240, 480, 720, 1440 e 2880 minutes after injection, 1 mL of blood was collected to delineate the pharmacokinetic profile of dextro-ketamine isolated or associated with midazolam by high performance liquid chromatography (HPLC) coupled to mass spectrometry. No animal had a negative response to nociceptive stimuli; however, the effects of DMO group were satisfactory for deep sedation. Only DI group did not presented HR alteration; in the other groups there was a significant decrease of this parameter. RR remained constant in all groups and T increased significantly only in DMC group. Pharmacokinetic analysis allowed determining the values of maximum concentration, area under the curve of plasma concentration-time, time to reach the maximum plasma drug levels, half-life, constant of elimination and clearance rate, and showed different values among groups in accordance with the route and administered drugs. We concluded the protocols cannot be used in surgical procedures. However, dextro-ketamine associated with midazolam injected in occipital venous sinus can be used for anesthesia induction and intracoelomic route can be used for application of dextro-ketamine alone for chemical restraint of Caiman crocodilus. Moreover, HPLC technique was effective in quantifying plasma levels of dextro-ketamine and midazolam of the species studied.

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HIRANO, L. Q. L. Contenção química e perfil farmacocinético da dextrocetamina, isolada em associação ao midazolam em jacaré-tinga Caiman crocodilus Linnaeus (1758) (Crocodylia: Alligatoridade). 2015. 87 f. Tese (Doutorado em Ciência Animal) - Universidade Federal de Goiás, Goiânia, 2015.