DELAYED RECOVERY FROM A SEDATIVE: CORRELATION OF THE PLASMA LEVELS OF DIAZEPAM WITH CLINICAL EFFECTS AFTER ORAL AND INTRAVENOUS ADMINISTRATION

Abstract
Plasma levels of diazepam were obtained in student volunteers after both oral and intravenous administration. Correlation with clinical effects showed that after oral administration, the onset of drowsiness and relaxation after 10–15 minutes was asso—ciated with a rapid absorption of the drug. When diazepam was administered intravenously, a pronounced clinical effect was observed for one hour after injection. This was followed by recovery at 2 hours, but subsequently the subjects reported recurrence of clinical symptoms at about 6 hours. This reappearance of drug action was shown to coincide with the remobilisation of diazepam in the subjea, supplemented by the slow build up of the metabolite Ro 5–2180 (desmethyldiazepam). It was not associated solely with the levels of Ro 5–2180. From these results it appears that patient recovery is not complete for several hours.