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Biomedical subjects

G D Olsen

Publications and source records attributed to G D Olsen.

56 records · Page 4Linked to original sources
PubMedDate not supplied

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.

Adult↗
PubMedDate not supplied

In vitro hepatic biotransformation of cocaine in maternal and fetal guinea pigs. Induction of cocaine N-demethylation with cocaine pretreatment.

In vitro N-demethylation of cocaine (COC) was examined in five saline (SAL) and five COC-treated pregnant guinea pigs and their fetuses (60 days, term 69 days). Microsomes from maternal and fetal guinea pigs produced norcocaine (NOR), benzoylnorecgonine (BN), and benzoylecgonine (BE) when incubated with COC. The initial rate of NOR formation was (mean +/- SE) 0.69 +/- 0.09 and 0.002 +/- 0.002 nmol/min/mg in microsomes from SAL-treated dams and their fetuses, respectively. The minimal fetal N-demethylation suggests BN seen previously in vivo after chronic maternal COC administration resulted from maternal formation of NOR and subsequent maternal or fetal hydrolysis to BN. COC pretreatment increased the initial rate of NOR formation to 1.38 +/- 0.28 nmol/min/mg (p < 0.05) and increased the extent of NOR formation by 12 min (p < 0.05). There was no change in total cytochrome P-450 concentrations in the dams. COC pretreatment had no effect on fetal hepatic N-demethylation of COC or total cytochrome P-450 content. The rate of NOR production plateaued in microsomes from both treatment groups by 20 min of incubation and could be restored when the microsomes were washed, repelleted, and reincubated. This suggests a soluble metabolite of COC inhibits COC N-demethylation. Microsomes from both SAL- and COC-treated animals produced this factor in the presence of COC, but the enzyme(s) responsible for COC N-demethylation in the SAL-treated pregnant guinea pig were more sensitive to inhibition than COC-pretreated animals.

Aminopyrine↗