Pharmacokinetics of hydromorphone hydrochloride after intravenous and intramuscular administration of a single dose to American kestrels (Falco sparverius)

David Sanchez-Migallon Guzman Veterinary Teaching Hospital, University of California-Davis, Davis, CA 95616.

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Butch KuKanich Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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Tracy L. Drazenovich Department of Veterinary Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

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Glenn H. Olsen Patuxent Wildlife Research Center, US Geological Survey, 12100 Beech Forest Rd, Ste 4039, Laurel, MD 20708.

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Joanne R. Paul-Murphy Department of Veterinary Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

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Abstract

Objective—To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in American kestrels (Falco sparverius).

Animals—12 healthy adult American kestrels.

Procedures—A single dose of hydromorphone (0.6 mg/kg) was administered IM (pectoral muscles) and IV (right jugular vein); the time between IM and IV administration experiments was 1 month. Blood samples were collected at 5 minutes, 1 hour, and 3 hours (n = 4 birds); 0.25, 1.5, and 9 hours (4); and 0.5, 2, and 6 hours (4) after drug administration. Plasma hydromorphone concentrations were determined by means of liquid chromatography with mass spectrometry, and pharmacokinetic parameters were calculated with a noncompartmental model. Mean plasma hydromorphone concentration for each time was determined with naïve averaged pharmacokinetic analysis.

Results—Plasma hydromorphone concentrations were detectable in 2 and 3 birds at 6 hours after IM and IV administration, respectively, but not at 9 hours after administration. The fraction of the hydromorphone dose absorbed after IM administration was 0.75. The maximum observed plasma concentration was 112.1 ng/mL (5 minutes after administration). The terminal half-life was 1.25 and 1.26 hours after IV and IM administration, respectively.

Conclusion and Clinical Relevance—Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.

Abstract

Objective—To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in American kestrels (Falco sparverius).

Animals—12 healthy adult American kestrels.

Procedures—A single dose of hydromorphone (0.6 mg/kg) was administered IM (pectoral muscles) and IV (right jugular vein); the time between IM and IV administration experiments was 1 month. Blood samples were collected at 5 minutes, 1 hour, and 3 hours (n = 4 birds); 0.25, 1.5, and 9 hours (4); and 0.5, 2, and 6 hours (4) after drug administration. Plasma hydromorphone concentrations were determined by means of liquid chromatography with mass spectrometry, and pharmacokinetic parameters were calculated with a noncompartmental model. Mean plasma hydromorphone concentration for each time was determined with naïve averaged pharmacokinetic analysis.

Results—Plasma hydromorphone concentrations were detectable in 2 and 3 birds at 6 hours after IM and IV administration, respectively, but not at 9 hours after administration. The fraction of the hydromorphone dose absorbed after IM administration was 0.75. The maximum observed plasma concentration was 112.1 ng/mL (5 minutes after administration). The terminal half-life was 1.25 and 1.26 hours after IV and IM administration, respectively.

Conclusion and Clinical Relevance—Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.

Contributor Notes

Supported by the Morris Animal Foundation (grant No. D10ZO-305).

Address correspondence to Dr. Sanchez-Migallon Guzman (guzman@ucdavis.edu).
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