Trough serum methadone concentration was measured in 43 patients under treatment for heroin addiction and complaining of withdrawal symptoms. Low serum levels were noted only in patients taking very low doses and in 10 patients who were concomitantly using enzyme-inducing drugs. The 27 patients in the maintenance program who had trough levels greater than 100 ng/ml were given no dose increase and were followed up prospectively. Alternate explanations for the patient's symptoms were well accepted in almost all cases, and subsequent performance in the treatment program appeared to be independent of serum level. We conclude that a trough serum level of 100 ng/ml is adequate for effective methadone maintenance. Measurement of serum levels can be a valuable intervention in patients with difficulties.

This study examined pharmacological factors contributing to persisting drug abuse by methadone maintenance clients. Three groups of clients, drawn from one treatment programme, were studied: persistent heroin users, persistent benzodiazepine users, and control subjects who were not using illicit drugs in addition to methadone. Persistent abusers mostly had high trough serum methadone levels, and their ongoing drug use appears to reflect a preference for a different drug effect rather than inadequate methadone dose. Several clients did have the expectation that methadone should prevent them from using other drugs; such expectations may diminish the effectiveness of treatment.

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It has been previously reported that treatment of urinary oxazepam by commercial β-glucuronidase enzyme preparations, from Escherichia coli, Helix pomatia and Patella vulgata, results in production of nordiazepam (desmethyldiazepam) artefact. In this study, we report that this unusual reductive transformation also occurs in other benzodiazepines with a hydroxyl group at the C3 position such as temazepam and lorazepam. As determined by liquid chromatography-mass spectrometry analysis, all three enzyme preparations were found capable of converting urinary temazepam into diazepam following enzymatic incubation and subsequent liquid-liquid extraction procedures. For example, when H. pomatia enzymes were used with incubation conditions of 18 h and 50 °C, the percentage conversion, although small, was significant--approximately 1% (0.59-1.54%) in both patient and spiked blank urines. Similarly, using H. pomatia enzyme under these incubation conditions, a reductive transformation of urinary lorazepam into delorazepam (chlordesmethyldiazepam) occurred. These findings have both clinical and forensic implications. Detection of diazepam or delorazepam in biological samples following enzyme treatment should be interpreted with care.

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