A possible diurnal variation in trazodone clearance.

Area of Science:

• Pharmacology
• Clinical Medicine
• Chronopharmacology

Background:

• Diurnal variations in drug metabolism are known for internal medicine drugs but not antidepressants.
• Long half-lives of most antidepressants can mask diurnal variations.
• Trazodone hydrochloride has a relatively short half-life, making it a candidate for studying diurnal variations.

Purpose of the Study:

• To investigate potential diurnal variations in serum levels of trazodone hydrochloride.
• To determine if co-administered medications influence these variations.

Main Methods:

• Serum trazodone levels were measured 11 hours after equal morning (9 a.m.) and evening (9 p.m.) doses.
• Participants had been on stable doses for over 3 days.
• Patients were analyzed both on trazodone alone and in combination with other medications.

Main Results:

• Serum trazodone levels were significantly higher in the morning (8 a.m.) compared to the evening (8 p.m.) for patients on trazodone with other medications (N=7, P<0.01).
• A similar trend approached statistical significance for patients on trazodone alone (N=8, P=0.06).

Conclusions:

• Trazodone hydrochloride may exhibit diurnal variations in serum levels, with higher concentrations observed in the morning.
• Co-administration of other medications, potentially through hepatic microsomal enzyme induction, may enhance these diurnal variations.