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Pharmacokinetics and pharmacodynamics of dermorphin in the horse
Author(s) -
Robinson M. A.,
Guan F.,
McDonnell S.,
Uboh C. E.,
Soma L. R.
Publication year - 2015
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12179
Subject(s) - dermorphin , pharmacokinetics , volume of distribution , pharmacodynamics , bioavailability , horse , chemistry , urine , pharmacology , medicine , endocrinology , opioid , receptor , opioid peptide , biology , paleontology
Dermorphin is a μ‐opioid receptor‐binding peptide that causes both central and peripheral effects following intravenous administration to rats, dogs, and humans and has been identified in postrace horse samples. Ten horses were intravenously and/or intramuscularly administered dermorphin (9.3 ± 1.0 μg/kg), and plasma concentration vs. time data were evaluated using compartmental and noncompartmental analyses. Data from intravenous administrations fit a 2‐compartment model best with distribution and elimination half‐lives (harmonic mean ± pseudo SD) of 0.09 ± 0.02 and 0.76 ± 0.22 h, respectively. Data from intramuscular administrations fit a noncompartmental model best with a terminal elimination half‐life of 0.68 ± 0.24 (h). Bioavailability following intramuscular administration was variable (47–100%, n = 3). The percentage of dermorphin excreted in urine was 5.0 (3.7–10.6) %. Excitation accompanied by an increased heart rate followed intravenous administration only and subsided after 5 min. A plot of the mean change in heart rate vs. the plasma concentration of dermorphin fit a hyperbolic equation (simple Emax model), and an EC 50 of 21.1 ± 8.8 ng/mL was calculated. Dermorphin was detected in plasma for 12 h and in urine for 48 or 72 h following intravenous or intramuscular administration, respectively.