Diazepam metabolism in normal man

It is demonstrated that serum concentrations obtained by administration of diazepam to normal subjects are dependent on the mode of administration. After intravenous injection the maximal level of about 1,600 ng per milliliter is reached in 15 minutes. Oral and intramuscular administration is followed by maximal levels of about 490 ng per milliliter in 30 minutes and of 290 ng per milliliter in 60 minutes, respectively. The clinical effects exhibited an accurate relationship to the serum concentration levels. At high levels of diazepam in the serum the sedative effect was accompanied by a marked deterioration of several mental functions and of coordination. Acute administration of single doses of diazepam did not produce significant amounts of the metabolite, N‐desmethyldiazepam, which therefore was unlikely to have contributed to the clinical effects.