title: Pharmacokinetics and pharmacodynamics of morphine in llamas.
abstract: 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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Samantha R
authors.initials: SR
authors.lastname: Uhrig
authors.forename: Mark G
authors.initials: MG
authors.lastname: Papich
authors.forename: Butch
authors.initials: B
authors.lastname: KuKanich
authors.forename: Khursheed R
authors.initials: KR
authors.lastname: Mama
authors.forename: Ann E
authors.initials: AE
authors.lastname: Wagner
authors.forename: Phillip L
authors.initials: PL
authors.lastname: Chapman
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hellyer
mesh_terms: 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
chemical_list: D000701:Analgesics, Opioid; D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine