Pharmacokinetics of trazodone sustained-release tablets in healthy subjects: Three open-label, randomized crossover studies .

Abstract

To characterize the pharmacokinetics of trazodone hydrochloride (HCl) sustained-release tablets (TSR) and trazodone immediate-release formulation (TIR) and investigate the effects of food on the pharmacokinetics of the drug in healthy subjects. Three open-label, randomized crossover trials of single-dose, multiple-dose, and food-drug interaction testing were conducted. A validated high-performance liquid chromatography-fluorescence method was used to measure the plasma concentration of trazodone, and a non-compartment model was used to obtain the pharmacokinetic parameters. AUC and Cmax dose proportionality were analyzed using a power model. TSR lacked dose proportionality over a dose range of 25 - 150 mg. In the food-drug interaction study, no significant changes in the pharmacokinetic parameters of the drug under the fed conditions were observed. Multiple dosage of TSR and TIR reached steady state after 7 days, with no accumulation phenomenon observed. The peak time and peak concentrations of TSR were significantly longer and lower, respectively, than those of TIR. TSR showed clear sustained-release characteristics, and food exhibited no significant effects on the pharmacokinetic parameters of trazodone. TSR and TIR reached steady state levels after 7 consecutive days of administration, with no accumulation phenomenon observed.