Pharmacokinetics and pharmacodynamics of dermorphin in the horse.
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.
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.|PA Equine Toxicology and Research Laboratory, West Chester, PA, USA.
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Robinson
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
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Guan
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
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McDonnell
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.|PA Equine Toxicology and Research Laboratory, West Chester, PA, USA.
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Uboh
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, USA.
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Soma
D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D019540:Area Under Curve; D005260:Female; D006207:Half-Life; D006736:Horses / Q000097:blood*; D008297:Male; D018847:Opioid Peptides / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D010865:Pilot Projects
D000701:Analgesics, Opioid; D018847:Opioid Peptides; C030058:dermorphin