Safety, tolerability, and pharmacokinetics of once-daily trazodone extended-release caplets in healthy subjects.

ABSTRACT

OBJECTIVE: To characterize the pharmacokinetics, safety, and tolerability of an extended-release formulation of trazodone hydrochloride (HCl), Trazodone Contramid® Once-a-Day (TzCOAD) developed as scored 150-mg and 300-mg caplets for oncedaily administration. METHODS: Relative bioavailability studies compared the pharmacokinetics of TzCOAD and trazodone immediate-release (TzIR) tablets following single- and multiple-dose administration. In addition, the effect of food on the pharmacokinetics of TzCOAD was assessed. RESULTS: After single-dose administration of 300 mg TzCOAD, trazodone AUC and C(max) were approximately 20% and 60% lower, respectively, than for TzIR 100-mg tablets administered as 3 doses, 8 h apart. After multipledose administration of 300 mg daily for 7 days, TzCOAD given once daily and TzIR given 3 times a day were equivalent with respect to AUC, while C(max) was 43% lower for TzCOAD. Trazodone AUC following single-dose administration of TzCOAD was similar to AUC at steady state, suggesting that steady-state exposure can be predicted from single-dose data. When TzCOAD was taken shortly after ingestion of a high-fat meal, C(max) increased 86% compared with fasting conditions. However, AUC and t(max) were not affected by food. CONCLUSION: Administration of TzCOAD 300 mg once daily provides equivalent steady-state exposure to, with a lower C(max) than, TzIR 100 mg given 3 times a day. A high-fat meal results in an increase in C(max), but there is no substantial effect on AUC.