The disposition of serum morphine following administration of 10 mg/70 kg was determined by a sensitive and specific radioimmunoassay in 31 anethetized surgical patients ranging in age from 23 to 75 yr. Following iv injection, 93 per cent of the morphine disappeared from the serum within 5 min. The early serum levels of the drug (2 min) correlated directly with the patients' ages (r equal to 0.63, p smaller than 0.01). Patient 23 to 50 yr of age averaged 0.29 mug/ml, whereas patients 51 to 75 ur of age averaged 70 percent higher, 0.49 mug/ml. The serum half-life between 10 and 240 min was independent of age and averaged about 2 hr after either iv or im administration. Following im admininstration, morphine was rapidly absorbed, with peak levels occurring within 10 to 20 min. The decline in morphine serum levels paralleled the decline in morphine analgesia and was coincident with the apperance of morphine glucuronide in the serum. These studies demonstrate the applicability and specificity of the radioimmunoassay for morphine and suggest that serum levels of morphine may be a useful and objective indicator of its pharmacologic activity.
Nitrous oxide produced a dose-related "analgesia" in mice (median effective dose, 55 percent). The analgesia was evaluated by means of a phenylquinone writhing test. Narcotic antagonists or chronic morphinization reduced nitrous oxide analgesia. Either nitrous oxide releases an endogenous analgesic or narcotic antagonists have analgesic antagonist properties heretofore unappreciated.
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