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  • Title: Relationship between EEG dynamics and pharmacokinetics of the benzodiazepine lormetazepam.
    Author: Kurowski M, Ott H, Herrmann WM.
    Journal: Pharmacopsychiatria; 1982 May; 15(3):77-83. PubMed ID: 6124982.
    Abstract:
    Clinical experience with benzodiazepines shows that observable effects like sedation do not persist as long as predicted by pharmacokinetic data. As a pharmacodynamic parameter closely related to effects of tranquillizers we used the quantitative pharmaco-EEG to compare time courses of these parameters with plasma level time courses. The subjects received single oral doses (1, 2 and 3 mg) of the benzodiazepine lormetazepam. Plasma levels were detected by radioimmunoassay. After fast absorption dose-dependent plasma level peaks could be determined 2 hours after administration. Applying an open two-compartment body model the drug was excreted with an elimination half-life of 10.3 hours. EEG power reached maximum changes after 1 hour in the delta, theta, alpha 2 and beta 1 frequency bands, as well as in the dominant alpha-frequency, and declined after that with different speeds to previous levels. Three to five hours after drug administration no significant changes could be detected. Vigilance sensitive EEG changes (delta, alpha 2) diminished earlier than indicated by plasma level half-lives. In contrast the decline of relative beta-power parallels plasma level time courses more closely under the 3 mg dose. In the present investigation, the computerized EEG appears to be a suitable indicator of monitoring time courses of sedative effects after single oral doses of benzodiazepines.
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