The purpose of this study was to compare the pharmacokinetic profiles at steady state of the test product, 300 mg trazodone hydrochloride (HCl) extended-release caplets (containing Contramid®), when administered once daily, and the reference product, 100 mg trazodone HCl immediate-release tablets (Apotex Corp.), when administered three times daily, for one week. For this purpose, the rate and extent of absorption of trazodone and formation of m-chlorophenylpiperazine (mCPP) after administration of multiple doses of up to 300 mg of each of the two formulations was compared.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Dosage form: Extended-release caplets containing 300 mg trazodone HCl and extended-release caplets containing 150 mg trazodone HCl (the 150 mg dosage form was only used for the up and down titration, and was not evaluated in the study). Dose regimen: 75 mg trazodone HCl (½ x 150 mg extended-release caplet) on Days 1 and 11, 150 mg trazodone HCl (one extended-release caplet) on Days 2 and 10, 300 mg trazodone HCl (one extended-release caplet) on Days 3 to 9, each at 23:30 after a fast of at least 4 hours.
Dosage form: Immediate-release tablet containing 100 mg trazodone HCl Dose regimen: 100 mg trazodone HCl (one immediate-release tablet) once (at 23:30) on Days 1 and 11, 100 mg trazodone HCl (one immediate-release tablet) twice (at 23:30 and 11:30) on Days 2 and 10, 100 mg trazodone HCl (one immediate-release tablet) three times daily (at 23:30, 07:30 and 15:30) on Days 3 to 9. Evening doses were administered after a fast of at least 4 hours.
Bioequivalence Based on Cmax,ss
Cmax,ss = Maximum plasma concentration (Cmax) at steady state (ss): (Cmax,ss). Measured in nanograms per milliliter (ng/mL).
Time frame: 9 days
Bioequivalence Based on AUCss
AUCss = Area under the plasma concentration curve (AUC) vs. time data pairs at steady state (ss): AUCss. Measured in nanograms x hours per milliliter (ng\*h/mL).
Time frame: 9 days
Minimum Plasma Concentration (Cmin,ss)
Minimum plasma concentration at steady state (Cmin,ss). Measured in nanograms per milliliter (ng/mL)
Time frame: 9 days
Plasma Concentration at 24 Hours Post-evening Dose (C24h)
Plasma concentration at 24 hours post-evening dose (C24h) in nanograms per milliliter (ng/mL)
Time frame: 9 days
Time to Peak Exposure (Tmax)
Time to peak exposure (Tmax) at steady state.
Time frame: 9 days
Percentage Swing
Percentage swing is a pharmacokinetic parameter calculated as follows: ((Cmax,ss - Cmin,ss)/Cmin,ss)\*100. Where: Cmax,ss = Maximum concentration at steady state; Cmin,ss = Minimum concentration at steady state. It was calculated over 24 hours on day 9.
Time frame: 9 days
Percentage Peak-Trough Fluctuation (%PTF)
Percentage Peak-Trough Fluctuation (%PTF) of trazodone calculated as \[100\*(Cmax-Cmin)/Cav\]. Cmax: Maximum plasma concentration Cmin: Minimum plasma concentration Cav: Average plasma concentration
Time frame: 9 days
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