Single- and multiple-dose pharmacokinetics and tolerability of paroxetine controlled-release tablet in healthy Chinese subjects

• Published in: International journal of clinical pharmacology and therapeutics Vol. 55; no. 3; pp. 231 - 236
• Main Authors: Chen, Rui, Shen, Kai, Hu, Pei
• Format: Journal Article
• Language: English
• Published: Germany Dustri - Verlag Dr. Karl Feistle GmbH & Co. KG 01.03.2017
• Subjects: Administration, Oral; Adult; Antidepressive Agents, Second-Generation - administration & dosage; Antidepressive Agents, Second-Generation - adverse effects; Antidepressive Agents, Second-Generation - blood; Antidepressive Agents, Second-Generation - pharmacokinetics; Anxiety; Area Under Curve; Asian People; Chromatography, Liquid; Delayed-Action Preparations; Drug Administration Schedule; Drug dosages; Female; Half-Life; Healthy Volunteers; Humans; Male; Metabolic Clearance Rate; Models, Biological; Paroxetine - administration & dosage; Paroxetine - adverse effects; Paroxetine - blood; Paroxetine - pharmacokinetics; Pharmacokinetics; Pharmacology; Plasma; Selective Serotonin Reuptake Inhibitors - administration & dosage; Selective Serotonin Reuptake Inhibitors - adverse effects; Selective Serotonin Reuptake Inhibitors - blood; Selective Serotonin Reuptake Inhibitors - pharmacokinetics; Tablets; Tandem Mass Spectrometry; Young Adult
• ISSN: 0946-1965
• DOI: 10.5414/CP202636

To evaluate the pharmacokinetics of paroxetine controlled-release (CR) tablets after single and multiple oral administrations and to evaluate its safety profile in healthy Chinese subjects. This was a phase 1, open-label, single- and multiple-dose combined study. All 12 healthy subjects received a single oral dose of 25-mg paroxetine CR, followed by a washout period of 5 days. Then, the subjects received multiple oral doses of 25-mg paroxetine CR for 14 consecutive days. Serial venous blood samples were collected 96 hours after single dosing and 24 hours after the last dose in multiple-dosing. Blood samples were analyzed using LC-MS/MS. Pharmacokinetic parameters of paroxetine were calculated via noncompartmental analysis using the WinNonlin software (Pharsight Corp., Mountain View, CA, USA). For both single- and multiple-dose regimens, a lag time of ~ 4 hours was observed before the absorption of paroxetine CR tablet with a t of ~ 7 - 9 hours. From single- to multiple-dose regimens, the mean C increased from 7.08 to 36.95 ng/mL, the mean AUC increased from 100.91 to 706.75 h×ng/mL, and the mean t increased from 12.3 to 83.6 hours (all p < 0.05). The point estimate and 90% confidence intervals of the C ratio indicated that the concentration of paroxetine reached steady state after 14 days of repeated dosing. The point estimate of the accumulation factor indicated that the extent of drug exposure at steady state was ~ 9 times that of single dosing. All reported adverse events were considered to be mild. Paroxetine CR tablet is absorbed with a delay of ~ 4 hours after oral administration, and the accumulation factor is ~ 9 at steady state. Paroxetine CR tablet is well tolerated by healthy Chinese subjects.
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