Pharmacokinetics of hydromorphone hydrochloride in healthy dogs.
OBJECTIVE
To assess the pharmacokinetics of hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs.


METHODS
Randomized experimental trial.


METHODS
Seven healthy male neutered Beagles aged 12.13 +/- 1.2 months and weighing 11.72 +/- 1.10 kg.


METHODS
The study was a randomized Latin square block design. Dogs were randomly assigned to receive hydromorphone hydrochloride 0.1 mg kg(-1) or 0.5 mg kg(-1) IV (n = 4 dogs) or 0.1 mg kg(-1) (n = 6) or 0.5 mg kg(-1) (n = 5) SC on separate occasions with a minimum 14-day washout between experiments. Blood was sampled via a vascular access port at serial intervals after drug administration. Serum was analyzed by mass spectrometry. Pharmacokinetic parameters were determined with computer software.


RESULTS
Serum concentrations of hydromorphone decreased quickly after both routes of administration of either dose. The serum half-life, clearance, and volume of distribution after IV hydromorphone at 0.1 mg kg(-1) were 0.57 hours (geometric mean), 106.28 mL minute(-1) kg(-1), and 5.35 L kg(-1), and at 0.5 mg kg(-1) were 1.00 hour, 60.30 mL minute(-1) kg(-1), and 5.23 L kg(-1), respectively. The serum half-life after SC hydromorphone at 0.1 mg kg(-1) and 0.5 mg kg(-1) was 0.66 hours and 1.11 hours, respectively.


CONCLUSIONS
Hydromorphone has a short half-life, suggesting that frequent dosing intervals are needed. Based on pharmacokinetic parameters calculated in this study, 0.1 mg kg(-1) IV or SC q 2 hours or a constant rate infusion of hydromorphone at 0.03 mg kg(-1) hour(-1) are suggested for future studies to assess the analgesic effect of hydromorphone.
KuKanich
Butch
B
PharmCATS and the Department of Anatomy and Physiology, Kansas State University, Manhattan, KS, USA.
Hogan
Brynn K
BK
Krugner-Higby
Lisa A
LA
Smith
Lesley J
LJ
D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D004285:Dogs; D006207:Half-Life; D004091:Hydromorphone / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male
D000701:Analgesics, Opioid; D004091:Hydromorphone