Temazepam clearance unaltered in cirrhosis.

Area of Science:

• Pharmacokinetics
• Hepatology
• Clinical Pharmacology

Background:

• Cirrhosis can alter drug metabolism and distribution.
• Benzodiazepine hypnotics like temazepam are commonly prescribed.
• Understanding temazepam's behavior in cirrhosis is crucial for patient safety.

Purpose of the Study:

• To evaluate the pharmacokinetics of a single oral dose of temazepam in patients with cirrhosis.
• To compare temazepam absorption, distribution, and elimination between cirrhotic patients and healthy controls.
• To assess the potential for temazepam accumulation in patients with cirrhosis.

Main Methods:

• Single oral dose pharmacokinetic study of temazepam.
• Comparison between nine patients with biopsy-proven cirrhosis and seven age/sex-matched healthy controls.
• Analysis of serum temazepam concentrations, volume of distribution, elimination half-life, clearance, and free fraction.

Main Results:

• Peak serum temazepam concentrations were reached significantly later in cirrhotics (2.9 h) versus controls (0.6 h), indicating slower absorption.
• No significant differences were observed in temazepam volume of distribution, elimination half-life, or clearance between groups.
• The free fraction of temazepam in serum was similar between cirrhotics and controls.

Conclusions:

• Temazepam absorption is delayed in patients with cirrhosis.
• The elimination rate and extent of accumulation of temazepam are not significantly altered in cirrhosis.
• The onset of temazepam's hypnotic activity may be delayed in cirrhotic patients, but its overall pharmacokinetic profile is largely preserved.