Pharmocokinetics and pharmacodynamics of single-dose triazolam: electroencephalography compared with the Digit-Symbol Substitution Test
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AIMS: To investigate whether the electroencephalogram (EEG) directly reflects the CNS effects of benzodiazepines by evaluating the relation of the EEG to plasma drug concentrations and to Digit-Symbol Substitution Test (DSST) scores after a single dose of triazolam, a representative benzodiazepine agonist. METHODS: Thirteen healthy male subjects were given 0.375 mg triazolam or placebo in a double-blind crossover study. Plasma samples were collected during 8 h after dosage. Pharmacodynamic effects were measured by DSST and EEG at corresponding times. RESULTS: Pharmacokinetic parameters for triazolam were consistent with established values. Compared with placebo, triazolam significantly impaired psychomotor performance on the DSST (P < 0.001) and increased beta amplitude on the EEG (P < 0.002). DSST and EEG changes both closely tracked changes in plasma concentrations over time. The changes for the two measures were highly correlated with each other (r =-0.94, P < 0.001) based on aggregate values at individual time points. However, the variations in area under the curve of pharmacodynamic effect vs. time (AUCeffect) measured by either method did not reflect the variations in plasma AUC across individuals. The individual variability in AUCeffect from the EEG was similar to that measured by the DSST. CONCLUSIONS: Both the EEG and the DSST reflect the central benzodiazepine agonist effects of triazolam. Intrinsic variability in both measures is similar.
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Compared with placebo, triazolam significantly impaired performance on the DSST (P < 0.001).
“Compared with placebo, triazolam significantly impaired performance on the DSST (P < 0.001) and increased beta amplitude on the EEG (P < 0.002).34”
From Digit Symbol Substitution Test: The Case for Sensitivity Over Specificity in Neuropsychological Testing (2018) · cites this paper as [34]
Both DSST and EEG changes closely tracked changes in plasma triazolam concentrations over time.
“Both DSST and EEG changes closely tracked changes in plasma triazolam concentrations over time.34”
From Digit Symbol Substitution Test: The Case for Sensitivity Over Specificity in Neuropsychological Testing (2018) · cites this paper as [34]
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- Authors
- Greenblatt, D. J., Gan, L., Harmatz, J. S., & Shader, R. I.
- Affiliations
- Tufts University (US)
- Corresponding author
- Greenblatt, David J.
- Venue
- British Journal of Clinical Pharmacology
- Publisher
- Wiley
- Published
- 2005-05-06
- Volume
- 60
- Issue
- 3
- Pages
- 244-248
- ISSN
- 0306-5251 (ISSN-L)
- 1365-2125
- PMC
- PMC1884767
- OpenAlex
- W2018089488
- Cited by
- 33
- References
- 18
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 2 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Clinical Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG-17880, R01AG017880)
- National Institute of Mental Health (MH 58435, R01MH058435)
- National Institute on Drug Abuse (DA 13834, R21DA013209, R01DA005258, R01DA013834, DA 13209, DA05258)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-58435)
- National Center for Research Resources (RR00054, M01RR000054)
- National Center for Complementary and Integrative Health (R01AT001381, AT01381)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Keywords
- triazolam, benzodiazepines, pharmacokinetics, pharmacodynamics, EEG, Digit Symbol Substitution Test, psychomotor performance, plasma drug concentration, interindividual variability
- MeSH terms
- Adult, Double-Blind Method, Electroencephalography, Humans, Male, Neuropsychological Tests, Psychomotor Performance, Symbolism, Triazolam, Cross-Over Studies, GABA Modulators
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