David V. Bowen

Drug interactions with methadone.

Chronic methadone maintenance is now being used to treat over 85,000 heroin addicts in the United States alone. It is also being widely used throughout the world. It has been suggested anecdotally that various sedatives, tranquilizers, other depressants and stimulants including alcohol, diazepam, barbiturates, cocaine and amphetamines may have additive, potentiating, or antagonistic effects when taken by methadone maintenance patients. Few of these postulated drug interactions have been documented in human subjects on chronic methadone maintenance. None of these pharmacologic agents have been shown to alter methadone disposition in patients receiving methadone on a chronic basis, although certainly such drug interactions might be documented in the future. Two different types of drug interactions, both resulting in the same clinical picture of acute narcotic withdrawal, have been observed in methadone-maintained subjects. Both of these drug interactions have been studied to determine whether or not the clinical observations of narcotic withdrawal could be related to any alterations in methadone disposition. Gas liquid chromatography techniques developed in this laboratory and chemical ionization mass spectrometry techniques developed in the collaborative laboratory were used in this study for the quantitative and qualitative analyses of methadone and its metabolites in plasma, urine, and feces. Following oral administration and absorption, methadone is widely distributed in the body. Plasma levels are relatively low, even after a chronic daily maintenance dose of 50 to 100 m ~ . l ~ Methadone is metabolized primarily in the liver by the hepatic microsomal drug-metabolizing enzymes. In the major pathway of biotransformation, methadone is first N-demethylated and then undergoes cyclization to form its major pyrrolidine metabolite (FIGURE 1) .4

Analyses of methadone and other drugs in maternal and neonatal body fluids: Use in evaluation of symptoms in a neonate of mother maintained on methadone

A former heroin addict treated with methadone maintenance throughout pregnancy, with rapid dose reduction from 110 mg to 9 mg during the last five weeks pre-partum, was evaluated in late pregnancy, at time of labor and delivery, and post-partum; her child was also evaluated. Using gas and thin-layer chromatography and mass spectroscopy, methadone levels were measured, and other drugs looked for in (1) plasma during late pregnancy, (2) mixed cord blood, (3) amniotic fluid at delivery, (4) maternal plasma and milk post-partum (on 50 mg methadone), (5) neonatal plasma and urine. Low levels of methadone were present in amniotic fluid and neonatal urine but not in mixed cord blood or neonatal plasma. Levels of methadone present in breast milk during moderate dose maintenance were also low. Unexpectedly, pentobarbital was identified in amniotic fluid. Neonatal infection was also diagnosed. Multiple factors may have contributed to symtoms observed in the neonate.

Gas chromatographic—mass spectrometric detection of circulating plasticizers in surgical patients

Gas chromatographic and gas chromatographic--mass spectrometric analytical techniques were employed to quantitate and confirm levels of circulating organic plasticizers in critically ill surgical patients. Two plasticizers, dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP), have been identified. DEHP can be found in many plastic medical devices. The DEHP levels were significant soon after transfusion or in the presence of renal dysfunction. The source of DBP is not clear at present and requires further study. The prevention of this contamination and the toxicity of these plasticizers should be investigated to ensure the safe use of plastic medical devices.