Studies on Metabolism of Trazodone, II. Metabolic Fate after Intravenous Administration and Effects on Liver Microsomal Drug-Metabolizing Enzymes in Rats

Abstract

1. The blood level of radioactivity following intravenous injection of [¹⁴C]-trazodone hydrochloride (4 mg/kg) decreases with three half-lives of 4.4 min, 49 min and 9.0 h.

2. The urinary and faecal excretions of radioactivity and the pattern of urinary and biliary metabolites after injection are approximately similar to those after oral administration.

3. A major metabolite of trazodone in rat bile and urine is the glucuronide conjugate of trazodone hydroxylated at C₄ of benzene ring.

4. The concentration of unchanged trazodone in rat brain is higher than that in plasma.

5. Trazodone HCl (80 mg/kg) administered intraperitoneally twice daily for 7 days to rats had no effect on liver weight, microsomal protein content, cyto-chrome P-450 content or on the metabolism of [¹⁴C]trazodone HCl and other substrates such as imipramine and aniline.