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Preliminary Pharmacokinetic Analysis of Tramadol and Its Metabolite O-Desmethyltramadol in Boa (Boa constrictor constrictor).

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Title: Preliminary Pharmacokinetic Analysis of Tramadol and Its Metabolite O-Desmethyltramadol in Boa (Boa constrictor constrictor).
Authors: Lopes Castro, Marina, Maldonado Moreno, Natalya, Wenceslau, Raphael Rocha, Paes Leme, Fabiola, Gonçalves, José Eduardo, Duque Estrada Meyer Fagundes, Lara, Fagundes, Natália, de Carvalho, Marcelo Pires Nogueira, Beier, Suzane Lilian
Source: Animals (2076-2615); Aug2025, Vol. 15 Issue 16, p2404, 12p
Subject Terms: PHARMACOKINETICS, LIQUID chromatography, DRUGS, DRUG administration, INTRAMUSCULAR injections, ANALGESIA, METABOLITES, PYTHONS
Abstract: Simple Summary: Tramadol is commonly used for pain relief in both humans and animals; however, its pharmacokinetics in reptiles, especially snakes, are not well understood. Pharmacokinetics refers to how a drug is absorbed, distributed, metabolized, and eliminated by the body over time. Ten healthy male Boa constrictor were given tramadol through two different methods: intramuscular injection and direct intravenous administration. Pharmacokinetics were analyzed using a liquid chromatography model. Chromatography is a physical method used to separate the components of a sample in order to identify and quantify them. The results showed that when tramadol was injected into the muscle, it was absorbed moderately well, with a significant amount of the drug and its active form remaining in the snakes' systems for a longer time. The observed sustained high concentrations of the active metabolite M1 suggest its potential as an analgesic in snakes. These findings suggest that tramadol could be an effective pain relief option for snakes. Understanding the pharmacokinetics of tramadol in these animals can help improve their health and welfare, ensuring they receive adequate pain management when needed. Boa constrictor snakes represent a suitable model for studying the absorption, metabolism, and elimination of tramadol due to their distinct physiological characteristics. The objective of this work was to provide preliminary data on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol (M1), in the plasma of Boa constrictor using liquid chromatography with fluorescence detection. Ten snakes received tramadol (5 mg kg−1) both into the epaxial musculature (TRIM) and into the paravertebral vein (TRIV) with a 45-day interval between the two administration methods. Blood samples were taken at specified time points to analyze the pharmacokinetics. Data were evaluated with an independent pharmacokinetic model (R software version 4.3.0). A paired Student's t-test was used for all parametric variables, except clearance, which was analyzed with the Wilcoxon test. A significance level of 5% was applied. The mean (range) maximum concentration of tramadol, volume of distribution, clearance, and elimination half-life for the TRIM group were 2.58 µg mL−1, 10.58 ± 2.91 L kg−1, 0.36 L kg−1 h−1, and 19.96 ± 8.34 h, respectively. For the TRIV group, these values were 3.39 µg mL−1, 5.60 ± 1.69 L kg−1, 0.22 L kg h−1, and 17.32 ± 7.55 h−1, respectively. M1 achieved maximum concentration and elimination half-lives of 0.58 µg mL−1 and 49.89 ± 10.8 h, respectively, for TRIM and 0.59 µg mL−1 and 35.66 ± 10.85 h for TRIV. The bioavailability of intramuscular tramadol was 61%, and M1 remained at similar concentrations for 20 min after tramadol administration in both treatments. Tramadol is rapidly biotransformed into M1 in Boa constrictors, maintaining high concentrations over an extended period. The pharmacokinetic characteristics, particularly the sustained plasma concentrations of M1, suggest potential for effective analgesia in the Boa constrictor. Furthermore, the intramuscular route provides the additional advantage of ease and practicality of administration. [ABSTRACT FROM AUTHOR]
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Database: Complementary Index
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Abstract:Simple Summary: Tramadol is commonly used for pain relief in both humans and animals; however, its pharmacokinetics in reptiles, especially snakes, are not well understood. Pharmacokinetics refers to how a drug is absorbed, distributed, metabolized, and eliminated by the body over time. Ten healthy male Boa constrictor were given tramadol through two different methods: intramuscular injection and direct intravenous administration. Pharmacokinetics were analyzed using a liquid chromatography model. Chromatography is a physical method used to separate the components of a sample in order to identify and quantify them. The results showed that when tramadol was injected into the muscle, it was absorbed moderately well, with a significant amount of the drug and its active form remaining in the snakes' systems for a longer time. The observed sustained high concentrations of the active metabolite M1 suggest its potential as an analgesic in snakes. These findings suggest that tramadol could be an effective pain relief option for snakes. Understanding the pharmacokinetics of tramadol in these animals can help improve their health and welfare, ensuring they receive adequate pain management when needed. Boa constrictor snakes represent a suitable model for studying the absorption, metabolism, and elimination of tramadol due to their distinct physiological characteristics. The objective of this work was to provide preliminary data on the pharmacokinetics of tramadol and its active metabolite, O-desmethyltramadol (M1), in the plasma of Boa constrictor using liquid chromatography with fluorescence detection. Ten snakes received tramadol (5 mg kg<sup>−1</sup>) both into the epaxial musculature (TRIM) and into the paravertebral vein (TRIV) with a 45-day interval between the two administration methods. Blood samples were taken at specified time points to analyze the pharmacokinetics. Data were evaluated with an independent pharmacokinetic model (R software version 4.3.0). A paired Student's t-test was used for all parametric variables, except clearance, which was analyzed with the Wilcoxon test. A significance level of 5% was applied. The mean (range) maximum concentration of tramadol, volume of distribution, clearance, and elimination half-life for the TRIM group were 2.58 µg mL<sup>−1</sup>, 10.58 ± 2.91 L kg<sup>−1</sup>, 0.36 L kg<sup>−1</sup> h<sup>−1</sup>, and 19.96 ± 8.34 h, respectively. For the TRIV group, these values were 3.39 µg mL<sup>−1</sup>, 5.60 ± 1.69 L kg<sup>−1</sup>, 0.22 L kg h<sup>−1</sup>, and 17.32 ± 7.55 h<sup>−1</sup>, respectively. M1 achieved maximum concentration and elimination half-lives of 0.58 µg mL<sup>−1</sup> and 49.89 ± 10.8 h, respectively, for TRIM and 0.59 µg mL<sup>−1</sup> and 35.66 ± 10.85 h for TRIV. The bioavailability of intramuscular tramadol was 61%, and M1 remained at similar concentrations for 20 min after tramadol administration in both treatments. Tramadol is rapidly biotransformed into M1 in Boa constrictors, maintaining high concentrations over an extended period. The pharmacokinetic characteristics, particularly the sustained plasma concentrations of M1, suggest potential for effective analgesia in the Boa constrictor. Furthermore, the intramuscular route provides the additional advantage of ease and practicality of administration. [ABSTRACT FROM AUTHOR]
ISSN:20762615
DOI:10.3390/ani15162404