Studies on morphine disposition: influence of general anaesthesia on plasma concentrations of morphine and its metabolites

The kinetics of morphine were studied during balanced anaesthesia in 10 patients undergoing lower abdominal or body surface surgery, and compared with those obtained in nine awake patients receiving morphine i.v. for the relief of chronic non-cancer pain. All patients received morphine sulfphate pentahydrate 10 mg i.v. over 30 s. Venous blood samples were collected for up to 180 min, and plasma concentrations of morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) assayed by a differential radioimmunoassay technique. There were no differences between groups with respect to the elimination half-life (awake group: 207 min; anaesthetized group: 153 min), volume of distribution at steady state (awake: 147 litre; anaesthetized: 128 litre), or clearance (awake: 587 ml min-1; anaesthetized: 766 ml min-1). Peak concentrations of M3G were similar in the two groups, but the peak concentration of M6G was greater in the anaesthetized patients. The AUC for M3G and M6G (0-180 min) also were greater in the anaesthetized patients, presumably as a result of decreases in renal blood flow and glomerular filtration rate during halothane anaesthesia.