Comparative Pharmacodynamics of Benzodiazepines
Dispositional pharmacokinetics have been shown to have little relationship to drug effects after acute doses of certain benzodiazepines (Ellinwood et al. 1983, 1985; Lader 1979; Ziegler et al. 1983). For diazepam the rapid onset of acute tolerance follows the peak behavioral effect; that is, impairment of performance in cognitive-neuromotor tests declines considerably faster than the corresponding serum drug concentration (Ellinwood et al. 1983, 1985). Other studies have described a relatively short period of impairment for high single doses of diazepam (George and Dundee 1977) and a more prolonged period of impairment for lorazepam (Seppala et al. 1976), although the elimination half-lives (t1/2) of diazepam and its active metabolite N-desmethyldiazepam (Mandelli et al. 1978) are over twice as long as that of lorazepam, which has no active metabolites.
KeywordsSerum Drug Concentration High Single Dose Digit Symbol Substitution Acute Tolerance Receptor Kinetic
Unable to display preview. Download preview PDF.
- Lader M (1979) Correlation of plasma concentrations of benzodiazepines with clinical effect. In: Priest RG, Pletscher A, Ward J (eds) Sleep research. MTP Press, LancasterGoogle Scholar
- Mandelli M, Tognoni G, Garattini S (1978) Clinical pharmacokinetics of diazepam. Clin Pharmacokinet 3: 72–91Google Scholar