Pharmacokinetics and Safety of Duloxetine Enteric-coated Tablets in Chinese Healthy Volunteers: A Randomized, Open-label, Single- and Multiple-dose Study

Abstract

Objective: Duloxetine hydrochloride is a selective serotonin (5-hydroxytryptamine) and norepinephrine reuptake inhibitor. It is approved for effective treatment for major depressive disorder. The pharmacokinetics (PK) of duloxetine has been studied, but few pharmacokinetics properties in Chinese subjects are available. This study explored the dose proportionality and determined duloxetine levels in human plasma by comparing the PK properties after administration of single or multiple doses in healthy volunteers. Methods: Thirty-six subjects were divided randomly into three groups and received a single dose of 15, 30, or 60 mg duloxetine. Those who received 30 mg continued on to the multiple-dose phase and received 30 mg daily for 7 days. Liquid chromatography/mass spectroscopy was applied to determine concentrations. The PK properties were calculated and included maximum plasma concentration (Cmax), time when maximum plasma concentration was reached (Tmax), time when half-maximum plasma concentration was reached (t1/2), area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0–t), mean concentration levels (AUC0-∞), and apparent total clearance of the drug from plasma after oral administration (CL/F). Results: The standard calibration curve was linear in the concentration range 0.11–112 ng/mL (r＞0.992). Linear PK properties were found at doses of 15–60 mg. The Cmax and AUC were proportional to dose, but the Tmax and t1/2 did not increase with increasing dose. Conclusion: No significant differences in the PK parameters were found among the three groups during the single-dose phase. The AUC and Cmax were greater in the multiple-dose phase, indicating duloxetine accumulation following multiple-dose administration.