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

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Abstract
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.
Funding Information
  • CAPES (Coordination for the Improvement of Higher Education Personnel)
  • Graduate Collegiate of the School of Veterinary Medicine at UFMG

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