Pharmacokinetics and pharmacodynamics of morphine in llamas.
OBJECTIVE
To assess the pharmacokinetics and pharmacodynamics of morphine in llamas.


METHODS
6 healthy adult llamas.


METHODS
Llamas received morphine sulfate in a randomized crossover design. In phase 1, they received IV or IM administration of morphine at 0.05 or 0.5 mg/kg, respectively; in phase 2, they received IV administration of morphine at 0.05, 0.25, or 0.5 mg/kg. Plasma morphine and morphine-6-glucuronide concentrations were determined by validated methods. Body temperature, heart rate, respiratory rate, sedation, and analgesia were assessed and compared with plasma concentrations by regression analysis.


RESULTS
Total body clearance was similar between IV administration of morphine sulfate at 0.25 and 0.5 mg/kg (mean +/- SD, 25.3 +/- 6.9 mL/min/kg and 27.3 +/- 5.9 mL/min/kg, respectively), and linearity was demonstrated between these doses. Bioavailability of morphine following IM administration at 0.5 mg/kg was 120 +/- 30%. Body temperature and sedation increased as the dose of morphine administered increased. Heart rate was unaffected by varying doses. Respiratory rate decreased as dose increased. Analgesia was difficult to assess as a result of high individual variability. Intravenous administration of morphine at 0.25 mg/kg provided the most consistent increase in tolerance to electric stimulation. Pharmacodynamic modeling revealed a sigmoidal relationship between plasma concentration and sedation score.


CONCLUSIONS
Morphine was characterized by a large apparent volume of distribution and high systemic clearance in llamas. A prolonged half-life was observed with IM injection. Intravenous administration of morphine sulfate at 0.25 mg/kg every 4 hours is suggested for further study.
Uhrig
Samantha R
SR
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Papich
Mark G
MG
KuKanich
Butch
B
Mama
Khursheed R
KR
Wagner
Ann E
AE
Chapman
Phillip L
PL
Hellyer
Peter W
PW
D000698:Analgesia / Q000379:methods / Q000662:veterinary*; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002161:Camelids, New World / Q000097:blood / Q000378:metabolism*; D018592:Cross-Over Studies; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007273:Injections, Intramuscular / Q000662:veterinary; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D009020:Morphine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D009022:Morphine Derivatives / Q000097:blood; D011897:Random Allocation; D012119:Respiration / Q000187:drug effects
D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine