Validation of a radioreceptor assay technique for monitoring pharmacological active material during intensive diazepam tetanus therapy.
The present study's aim was to monitor the daily plasma levels of diazepam and its metabolites in two tetanic patients who were receiving very strong doses of diazepam in continuous infusion. The kinetics of high doses of diazepam were estimated. These plasma levels were determined selectively using gas-liquid chromatography (GLC), then correlated with a global estimation by radioreceptor-assay (RRA). At the end of the infusion, the kinetics of diazepam and of RRA active material were calculated using a linear, open, two compartment model. Muscle-relaxant and residual sedative effects were clinically monitored. The mean concentrations of diazepam (2.33, 0.60 micrograms/ml), desmethyldiazepam (3.27, 1.00 micrograms/ml) and oxazepam (0.73, 0.47 micrograms/ml) estimated by GLC and of RRA active material (5.62, 1.08 micrograms/ml) correlated better when active metabolites were considered (r = 0.898) than when diazepam alone was taken into account (r = 0.730), indicating that these metabolites influence the overall activity of the parent compound. Half-lives of RRA results (52.6 h for patient 1 and 82.5 h for patient 2) were higher than those of diazepam estimated using GLC results (21.2 h for patient 1 and 42.3 h for patient 2). This could be related to the contribution of the active metabolites and might explain the residual sedative effect observed for at least seven days following cessation of the diazepam (DZP) infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
D001711:Biotransformation; D002849:Chromatography, Gas; D002927:Cimetidine / Q000627:therapeutic use; D003975:Diazepam / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007700:Kinetics; D008875:Middle Aged; D003708:Nordazepam / Q000097:blood; D010076:Oxazepam / Q000097:blood; D011869:Radioligand Assay; D013742:Tetanus / Q000097:blood* / Q000188:drug therapy
D003708:Nordazepam; D010076:Oxazepam; D002927:Cimetidine; D003975:Diazepam