Centrally administered codeine glucuronide has been shown to exhibit antinociceptive properties with decreased immunosuppressive effects compared to codeine. In this study, codeine-6-glucuronide was administered to rats, and its analgesic effect was compared to that of codeine. The concentrations of codeine and its metabolites in plasma and brain were also determined at the peak response time after administration of each compound. Receptor-binding studies with rat brain homogenates and affinity profiles were also determined. Intravenous administration of codeine-6-glucuronide resulted in approximately 60% of the analgesic response elicited by codeine itself. Analysis of plasma and brain showed that codeine-6-glucuronide is relatively stable in vivo, with only small amounts of morphine-6-glucuronide being detected in addition to unchanged codeine-6-glucuronide. The receptor affinity of codeine-6-glucuronide was similar to that of codeine. It is concluded that intravenously administered codeine-6-glucuronide possesses analgesic activity similar to that of codeine, and may have clinical benefit in the treatment of pain
The objective of this study was to measure and compare the serum concentrations of dexamethasone after oral and transdermal administration using pluronic lecithin organogel in six healthy cats. The study was designed as a crossover, in which the cats were randomly assigned to two groups. The cats received a single dose (0.05 mg kg(-1)) of dexamethasone either orally or transdermally on the inner pinna. Blood samples were taken at 0, 5, 15, 30, 60, 90 and 120 min, and 3, 4, 6, 8, 12 and 24, 48 and 72 h post dexamethasone administration. A mean peak serum concentration of 30.1 ng mL(-1) was detected 15 min after oral administration. Serum concentrations were below detection limits by 24 h. In contrast, there was no significant increase in serum concentrations of dexamethasone after transdermal administration. In cats, transdermal administration of a single dose of dexamethasone did not result in significant serum concentrations compared to oral administration.
The increased use of cocaine by women of child-bearing age has left many health care scientists searching for improved methods of detecting prenatal cocaine exposure. To that end, a study of the determination of cocaine and its metabolites in amniotic fluid and umbilical cord tissue was undertaken. Amniotic fluid (n = 32) and umbilical cord tissue (n = 70) specimens were collected from pregnant subjects admitted to labor and delivery at Shands Hospital at the University of Florida (Gainesville, FL). Subjects were interviewed regarding drug use during each trimester. Subjects reporting cocaine use were designated as target subjects, and those denying use were control subjects. The specimens were subjected to solid-phase extraction and analyzed for cocaine and its metabolites by gas chromatography-mass spectrometry. Cocaine analytes (predominantly benzoylecgonine) were detected in 28.1 and 18.5% of the amniotic fluid and umbilical cord tissue specimens, respectively. Other cocaine analytes frequently detected included ecgonine methyl ester and m-hydroxy-benzoylecgonine in amniotic fluid specimens and ecgonine methyl ester, norcocaine, and m-hydroxybenzoylecgonine in umbilical cord tissue specimens. This study has shown that cocaine and its metabolites are readily detected in specimens of maternal and fetal origin.
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