Background: To investigate the pharmacokinetics of single dose morphine inhaled by modified ultrasonic nebulizer versus intravenous administered in ventilated dogs.
Methods: Six healthy dogs were randomly assigned to receive nebulized or intravenous morphine and crossed over to the alternative medication 1 week after. Morphine was nebulized by modified ultrasonic nebulizer (YuYue 402A, Jiangsu, China). Arterial blood was sampled every minute during the 10 min of administration and at 2, 5, 7, 10, 15, 20, 45, 60, 90, 120, 150, 180, 240, and 360 min after the administration for the determination of morphine concentration by RP-HPLC.
Results: The main pharmacokinetic parameters of morphine by inhaled and intravenous administration were: MRT 59±14 min versus 19±4 min, T(1/2) 21.9±5.1 min versus 3.3±1.0 min, T(max) 23.0±2.7 min versus 8.8±2.4 min, C(max) 0.245±0.09 mg·L⁻¹ versus 1.09±0.32 mg·L⁻¹, AUC(0-∞) 9.7±1.1 mg·min·L⁻¹ versus 15.2±7.2 mg·min·L⁻¹, CL 0.069±0.019 L·min⁻¹·kg⁻¹ versus 0.063±0.028 L·min⁻¹·kg⁻¹, and the absolute bioavailability of inhaled morphine was 35.5±10%. There were no significant differences (p<0.05) between inhaled and intravenous morphine in AUC and CL. As expected, the T(½) and MRT of inhaled morphine were significantly greater than those of intravenous morphine.
Conclusions: Morphine nebulized by ultrasonic nebulizer can be rapidly and extensively absorbed by lungs in ventilated dogs.