Pharmacokinetics of acetaminophen, codeine, and the codeine metabolites morphine and codeine-6-glucuronide in healthy Greyhound dogs
2010
KuKANICH, B.
KuKanich, B. Pharmacokinetics of acetaminophen, codeine, and the codeine metabolites morphine and codeine-6-glucuronide in healthy Greyhound dogs. J. vet. Pharmacol. Therap. 33, 15-21. The purpose of this study was to determine the pharmacokinetics of codeine and the active metabolites morphine and codeine-6-glucuronide after i.v. codeine administration and the pharmacokinetics of acetaminophen (APAP), codeine, morphine, and codeine-6-glucuronide after oral administration of combination product containing acetaminophen and codeine to dogs. Six healthy Greyhound dogs were administered 0.734 mg/kg codeine i.v. and acetaminophen (10.46 mg/kg mean dose) with codeine (1.43 mg/kg mean dose) orally. Blood samples were collected at predetermined time points for the determination of codeine, morphine, and codeine-6-glucuronide plasma concentrations by LC/MS and acetaminophen by HPLC with UV detection. Codeine was rapidly eliminated after i.v. administration (T[fraction one-half] = 1.22 h; clearance = 29.94 mL/min/kg; volume of distribution = 3.17 L/kg) with negligible amounts of morphine present, but large amounts of codeine-6-glucuronide (Cmax = 735.75 ng/mL) were detected. The oral bioavailability of codeine was 4%, morphine concentrations were negligible, but large amounts of codeine-6-glucuronide (Cmax = 1952.86 ng/mL) were detected suggesting substantial first pass metabolism. Acetaminophen was rapidly absorbed (Cmax = 6.74 μg/mL; Tmax = 0.85 h) and eliminated (T[fraction one-half] = 0.96 h). In conclusion, the pharmacokinetics of codeine was similar to other opioids in dogs with a short half-life, rapid clearance, large volume of distribution, and poor oral bioavailability. High concentrations of codeine-6-glucuronide were detected after i.v. and oral administration.
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