Pharmacokinetics and safety of paroxetine controlled-release tablet in healthy Chinese subjects: a single-dose three-period crossover study

Objectives: To evaluate the pharmacokinetics of paroxetine controlled release tablets after single oral administrations and its safety profile in healthy Chinese subjects. Methods: This was a phase I, open label, single-dose, three-period crossover study in which 12 healthy subjects received single oral doses of 12.5, 25, 37.5 mg paroxetine controlled-release tablets with 10 day washout between doses. Serial venous blood samples were collected for 96 hours after study drug administration and analyzed with LC-MS/MS. Pharmacokinetic parameters of paroxetine were calculated using non-compaitinental analysis with Win-Nonlin software. Results: The absorption of controlled-release paroxetine was delayed with a median t(max) of 8 10 hours and the mean t(1/2) was 12 - 14 hours across all doses. Over the dose range of 12.5 - 37.5 mg, the mean C-max increased from 2.62 to 15.13 ng/mL and AUC(0-infinity) increased from 63.56 to 404.91 hxng/mL. The 90% CI for the ratio of dose-normalized mean values of Cmax and AUC were not contained within the criteria limits, indicating a greater than dose proportional increase. All reported adverse events were considered to be mild. Conclusions: Plasma exposure of controlled-release paroxetine increased with dose escalation, but linear pharmacokinetics were not observed over the studied doses. Paroxetine controlled-release tablet was well tolerated in healthy Chinese subjects.