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Master's Dissertation
DOI
10.11606/D.10.2018.tde-12072018-122425
Document
Author
Full name
Vanessa Nadine Gris
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2018
Supervisor
Committee
Cortopassi, Silvia Renata Gaido (President)
Carregaro, Adriano Bonfim
Ciscato, Cláudia Helena Pastor
Title in Portuguese
Avaliação dos efeitos antinociceptivos e farmacocinética do tramadol em jabutis-piranga
Keywords in Portuguese
Chelonoidis carbonarius
Antinocicepção
CG-MS/MS
Opioide
Répteis
Abstract in Portuguese
O tramadol é um analgésico de ação central amplamente utilizado em répteis. Seu efeito ocorre por meio da ativação de receptores opioides e do bloqueio da recaptação de serotonina e norepinefrina. Este estudo objetivou avaliar a atividade antinociceptiva e a farmacocinética do tramadol em jabutis-piranga. Oito jabutis receberam quatro tratamentos, com intervalo mínimo de 21 dias: solução salina (grupo controle), tramadol nas doses de 5 mg/kg (TIM5) e 10 mg/kg (TIM10) por via intramuscular e 5 mg/kg (TIV5) por via intravenosa. Um estímulo nociceptivo térmico foi aplicado na superfície plantar dos animais e a avaliação da latência do reflexo de retirada do membro foi realizada nos tempos 0, 30 minutos, 1, 2, 4, 6, 8, 10, 24, 48, 72 e 96 horas. Foi realizada também colheita de sangue e análise do plasma por meio de cromatografia gasosa acoplada à espectrometria de massas triplo quadrupolo. A farmacocinética do tramadol foi calculada por abordagem não-compartimental. A concentração máxima para TIM5 e TIM 10 foi de 128,98 ± 59,46 ng/mL e 613,87 ± 524,26 ng/mL, respectivamente. A meia-vida de eliminação foi de 21,22 ± 8,74 horas para TIV5, 32,84 ± 6,41 horas para TIM5 e 22,5 ± 8,02 horas para TIM10. As doses de tramadol 10 mg/kg por via intramuscular e 5 mg/kg por via intravenosa não apresentaram alteração do tempo de latência para o reflexo de retirada do membro. O grupo que recebeu 5 mg/kg por via intramuscular apresentou diferença nos tempos 1 hora e 24 horas após a administração. O tramadol não apresentou efeito antinociceptivo consistente por via intramuscular nas doses de 5 e 10 mg/kg e por via intravenosa na dose de 5 mg/kg em jabutis-piranga. Independente da via de administração, o tramadol apresentou meia-vida de eliminação longa.
Title in English
Evaluation of the antinociceptive effects and pharmacokinetics of tramadol in red-footed tortoises
Keywords in English
Chelonoidis carbonarius
Antinociception
GC-MS/MS
Opioid
Reptiles
Abstract in English
Tramadol is a centrally acting analgesic widely used in reptiles. It promotes activation of opioid receptors and inhibits serotonin and norepinephrine reuptake. This study aimed to evaluate the antinociceptive effects and pharmacokinetics of tramadol in red-footed tortoises. Eight animals were treated with four different protocols, with a 3-week washout period: saline IM (control group), tramadol 5 mg/kg IM (TIM5) and 10 mg/ kg IM (TIM10) and 5 mg/kg IV (TIV5). Infrared heat stimuli was applied to the plantar surface of the animals and thermal withdrawal latencies were measured at 0 and 30 minutes, 1, 2, 4, 6, 8, 10, 24, 48, 72 and 96 hours after drug treatment. Blood samples were obtained and plasma analysis performed by gas chromatography - triple quadrupole tandem mass spectrometry. Pharmacokinetics parameters were determined using non-compartimental equations. The average peak drug concentration was 128.98 ± 59.46 ng/mL (TIM5) and 613.87 ± 524.26 ng/mL (TIM10). The elimination half-life was 21.22 ± 8.74 hours (TIV5), 32.84 ± 6.41 hours (TIM5) and 22.5 ± 8.02 hours (TIM10). TIM10 and TIV5 showed no changes in thermal withdrawal latencies. TIM5 showed a significant increase in thermal withdrawal latencies at 1 hour and 24 hours after administration. Tramadol did not induce a consistent antinociceptive effect at 5 mg/kg and 10 mg/kg IM and ar 5 mg/kg IV in red-footed tortoises. Regardless of the route of administration, tramadol had a long half-life and plasma concentrations close to those reported in other species.
 
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Release Date
2020-08-22
Publishing Date
2018-10-29
 
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