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Abstract
This study was performed in order to correlate changes in blood levels of diazepam and desmethyldiazepam with the symptomatology of withdrawal and to examine their elimination kinetics in abusers.
The determined half-life of desmethyldiazepam in five diazepam abusers had a wide range of 46.2 to 94.5 hours. Two episodic very high dose abusers exhibited shorter desmethyldiazepam half-1ives than was considered normal, possibly due to auto-induction. The half-life of diazepam in a documented very high dose user exceeded that reported in the literature, probably due to accumulation.
Withdrawal symptoms reported by the subjects were moderate and included some mental confusion. The most distressing symptom reported was dramatic mood swings which occurred over a matter of minutes.
The disappearance of diazepam from blood appears to be the initial cause of withdrawal. Desmethyldiazepam may moderate the severity of the abstinence syndrome but probably lengthens the withdrawal process.
a The TLC plates were Analteck Silica Gel GF, 250 micron, 20 × 20 cm, obtained from Analtech, Newark, Delaware. The mobi1e phase was chloroform/aceton2(9:l). The solvents were prepared daily and allowed to equilibrate in a lined TLC tank for one-half hour before use.
b The gas chromatograph was a Hewlett-Packard Model 5830A (Hewlett-Packard, Avondal e, Pennsylvania), equipped with a nitrogen-phosphorous s ensitive detector and a glass column, 120 cm × 2 mm i.d., containing 3% OV-1 on 8 0/100 mesh chromosorb W-HP. Oven temperature was 225′. He1ium (carrier) was 30 mL/min. Hydrogen and air flows were 3 and 50 mL/min, respectively and collector voltage was 16V.