Pharmacokinetic profiles of three dose rates of morphine sulfate following single intravenous, intramuscular, and subcutaneous administration in the goat

Abstract

This study aimed to evaluate pharmacokinetic profiles of morphine in goats following a single dose administered intravenously, intramuscularly, or subcutaneously at 0.1 mg/kg, 0.25 mg/kg, and 0.4 mg/kg. Study population included eight healthy adult goats in a randomized cross‐over study. Serial plasma samples were collected and morphine was quantified using high‐performance liquid chromatography/mass spectrometry. Data fit a two‐compartment model following intravenous administration and a non‐compartmental model following both intramuscular and subcutaneous administration. Plasma elimination half‐life was 2.88 ± 1.13 h (0.1 mg/kg), 2.30 ± 0.49 h (0.25 mg/kg), and 2.67 ± 0.82 h (0.4 mg/kg) following IV morphine. Intramuscular Cmax values were 13.4 ± 2.77 ng/ml (0.1 mg/kg), 34 ± 11.50 ng/ml (0.25 mg/kg), and 68.9 ± 24.5 ng/ml (0.4 mg/kg). Intramuscular Tmax f(h) or IM dosing (in hrs) was 0.19 ± 0.14 (0.1 mg/kg), 0.24 ± 0.24 (0.25 mg/kg), and 0.21 ± 0.24 (0.4 mg/kg). Subcutaneous Cmax values were 9.88 ± 3.31 ng/ml (0.1 mg/kg), 28.5 ± 11.6 ng/ml (0.25 mg/kg), and 39.4 ± 14.3 ng/ml (0.4 mg/kg). Subcutaneous Tmax (h) values for SC dosing were 0.36 ± 0.21 (0.1 mg/kg), 0.31 ± 0.17 (0.25 mg/kg), and 0.4 ± 0.13 (0.4 mg/kg). Intramuscular bioavailability values were 153.77 ± 12.60% (0.4 mg/kg), 104.8 ± 25.12% (0.25 mg/kg), and 100.7 ± 29.57% (0.1 mg/kg). Subcutaneous bioavailability values were 130.58 ± 19.07% (0.4 mg/kg), 116.6 ± 27.03% (0.25 mg/kg), and 111.6 ± 23.24% (0.1 mg/kg). No adverse effects were observed. Assuming plasma concentration required to induce analgesia is 16 ± 9 ng/ml in goats, as demonstrated in humans, it is suggested to administer morphine intramuscularly at 0.4 mg/kg every 3–4 h or SC every 2–3 h. This is a speculative conclusion therefore further studies evaluating pharmacodynamics and plasma analgesic threshold in goats is recommended.

Pharmacokinetics of butorphanol following intravenous and intramuscular administration in donkeys: A preliminary study

“…Alternatively, it could be due to inter-individual variability in the rate of absorption as some individuals did not adhere to expected rise and fall from the IM administration. A bioavailability of >100% for morphine has been reported in goats (30), llamas (31), and dogs (32) and this could be attributed to a limited or minimal distribution phase.…”