SummaryThe effect of hydrogen, chloride and calcium ions on the binding of diazepare to human serum albumin has been studied by circular dichroism and equilibrium dialysis. In all cases the molar ellipticity of the diazepam-albumin complex increases with pH over the pH range 5 to 9. Under these conditions the free concentration of diazepam at a constant low drug to protein ratio decreases with pH. This free concentration is higher in the presence of chloride and calcium ions. With a two state conformational model for albumin it was shown, that the pH dependences of molar ellipticity of the diazepam-albumin complex and of the free concentration of diazepam are linked. It was demonstrated that the N-B transition of albumin is involved in the pH dependent binding of diazepam. The consequences of these findings for equilibrium dialysis procedures in determining free plasma levels of diazepam are discussed.

The primary aim of this study was to compare task performance in a laboratory test and real driving performance of outpatients receiving diazepam medication with those of control subjects. Plasma and saliva samples were taken to investigate a level-response relationship. Real driving performance was measured by trained observers. The design of the laboratory test was based on a vigilance task (high attention) directly followed by a simple eye-hand coordination tasks (low attention). Twenty-two males participated in the study. Diazepam was given orally by prescription, mostly as a maintenance dose of 5 mg three times a day. Patients receiving diazepam showed impaired performance in the driving test and the low-attention task. Furthermore, the results indicate no relationship between plasma or saliva levels of diazepam and/or its metabolite N-desmethyldiazepam and real driving performance and/or laboratory task performance.

1 Salivary, unbound and total plasma levels of diazepam have been compared in nineteen subjects. 2 Salivary diazepam levels were significantly higher (P < 0.001) than, but closely related to the corresponding unbound levels (r = 0.97) at 2.5‐3 h after administration of the drug. 3 The results presented suggest that saliva levels can be used to predict the corresponding plasma levels at a given time, but there is no 1:1 relation between the unbound diazepam concentration in plasma and the saliva level of the drug.

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