Abstract
OBJECTIVE: To investigate the analgesic and nonanalgesic effects and the pharmacokinetics of an intravenous infusion of 2 mg hydromorphone over 20 mins.DESIGN: Open study.SUBJECTS: Twelve healthy volunteers.MEASUREMENTS: The analgesic effect of hydromorphone was evaluated serially using pressure pain thresholds (PPTs) measured on the third fingers and toes. The nonanalgesic effects of hydromorphone were measured as miosis, decrease of saliva production and central nervous effects such as euphoria/dysphoria, nausea, headache, fatigue and feeling of heaviness. Plasma concentration of hydromorphone was measured using high performance liquid chromatography.RESULTS: PPTs were significantly increased compared with baseline levels for up to 2 h after the infusion of hydromorphone. Significant miosis and reduction of saliva production were registered up to 6 h after drug administration. Fatigue and heaviness were reported by all subjects. In the studied opioid-naive subjects, the hydromorphone-induced analgesic effect was of shorter duration than the studied nonanalgesic effects. The terminal elimination half-life of hydromorphone was 1.87±0.4 h (± SD) (95% CI 1.61 to 2.13), systemic clearance was 1.81±0.25 L/min (95% CI 1.65 to 1.97) and volume of distribution was 4.15±0.86 L/kg (95% CI 3.6 to 4.71).CONCLUSION: Analgesia and nonanalgesic effects appear to be well correlated with the plasma concentrations of the hydromorphone.