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The secretion of methadone and its major metabolite in the gastric juice of humans: comparison with blood and salivary concentrations.

Four healthy subjects and four addicts on high daily maintenance doses of methadone each received a parenteral dose of methadone hydrochloride following an overnight fast. The concentration of methadone in blood was compared with that in the gastric juice obtained over 8 hr by continuous low-pressure suction via a nasogastric tube. The concentration in the gastric juice was 25-200 times that measured at the same time in the blood. Thus, 8 hr after the injection mean blood concentrations of 28 and 210 ng of methadone per ml were recorded in the normal subjects and the addicts, respectively. The corresponding concentrations in gastric juice were 2,200 ng/ml and 18,000 ng/ml, respectively. In the normal subjects about 2% of the administered dose was recovered in the gastric juice in 8 hr, whereas in addicts about 7% was recovered. The greater recovery of methadone from the addicts appears to be the result of the larger volume of gastric juice recovered from the latter subjects. Methadone was also excreted in the saliva of both groups of subjects. In addicts, salivary concentrations were often 10 times those recorded in the blood. The N-monodemethylated metabolite of methadone was identified in the gastric juice of addicts by gas chromatography and mass spectrometry.