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Oxidative versus conjugative biotransformation of temazepam
1Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.
Biopharmaceutics & Drug Disposition
|August 1, 1990
Summary
Temazepam is primarily cleared by direct glucuronide conjugation, with temazepam glucuronide excreted in urine. A smaller pathway involves oxidation to oxazepam, then conjugation and excretion.
Area of Science:
- Pharmacokinetics
- Drug Metabolism
- Clinical Pharmacology
Background:
- Benzodiazepine hypnotics like temazepam are widely used for insomnia.
- Understanding temazepam's metabolic pathways and excretion is crucial for optimizing its clinical use.
- Previous studies have suggested multiple routes for temazepam metabolism.
Purpose of the Study:
- To quantify the pharmacokinetic profile of temazepam in healthy volunteers.
- To determine the primary metabolic and excretion pathways of temazepam.
- To investigate the relationship between body weight and temazepam pharmacokinetics.
Main Methods:
- Single oral dose administration of 30 mg temazepam to 24 healthy volunteers.
- Plasma sampling over 48 hours to measure intact temazepam levels.
- Urine collection over 48 hours to measure intact temazepam, temazepam glucuronide, and oxazepam glucuronide.
Main Results:
- Mean elimination half-life of temazepam was 9.9 hours.
- Volume of distribution significantly increased with body weight (r = 0.67).
- 39% of the dose was recovered as temazepam glucuronide in urine, indicating direct conjugation as a major clearance pathway.
Conclusions:
- Temazepam clearance is significantly driven by direct glucuronide conjugation.
- Oxidation to oxazepam followed by glucuronidation represents a minor metabolic pathway.
- Body weight influences temazepam's volume of distribution and peak plasma levels.