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Time-dependent sensitization to triazolam? An observation in three studies
P D Kroboth1, J W McAuley, C L Derry
1Department of Pharmacy and Therapeutics, University of Pittsburgh, Pennsylvania, 15261, USA.
Journal of Clinical Psychopharmacology
|June 1, 1995
Summary
Time-dependent sensitization (TDS) to triazolam was observed in clinical studies. Repeated dosing at weekly intervals increased drug response per unit of triazolam concentration, suggesting a need for further investigation.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Neuroscience
Background:
- Triazolam is a benzodiazepine used for insomnia.
- Previous studies have not extensively investigated the potential for time-dependent sensitization to triazolam with repeated dosing intervals.
Purpose of the Study:
- To investigate the phenomenon of time-dependent sensitization (TDS) to triazolam.
- To analyze the relationship between triazolam concentration and psychomotor/sedation effects over time.
Main Methods:
- Three clinical studies involving healthy male subjects were analyzed.
- Subjects received varying doses of triazolam intravenously or orally at weekly intervals.
- Pharmacokinetics and psychomotor responses (Digit Symbol Substitution Test, Continuous Performance Test) were assessed. Sedation was also rated.
Main Results:
- Effect ratios, representing response relative to plasma drug concentration, increased progressively over weeks for the Continuous Performance Test (CPT).
- Increases in effect ratios ranged from 31.9% to 631% across studies, indicating enhanced responsiveness per unit of triazolam concentration.
- Similar trends were observed for other psychomotor and sedation measures.
Conclusions:
- Data suggest an emergent time-dependent sensitization to triazolam with single doses administered at weekly intervals.
- The findings were incidental observations but warrant dedicated studies to confirm this sensitization phenomenon.