Open label, three period, single sequence, study of 5, 25, 50 mg sertraline pharmacokinetics in healthy male Korean volunteers
| Autor: | Sumin Yoon, In-Jin Jang, Kyung Sang Yu, Sukyoun Shin, Joo Youn Cho, Kwan Kim, Myoung Kyu Park, Tae Eun Kim, Kyusoon Shin |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Pharmacology Sertraline Korea Dose-Response Relationship Drug business.industry Microdosing Cmax Middle Aged Single sequence Young Adult Pharmacokinetics Obsessive compulsive Area Under Curve Humans Medicine Pharmacology (medical) Dosing Open label business Selective Serotonin Reuptake Inhibitors medicine.drug |
| Zdroj: | Int. Journal of Clinical Pharmacology and Therapeutics. 49:672-678 |
| ISSN: | 0946-1965 |
| DOI: | 10.5414/cp201578 |
| Popis: | BACKGROUND Sertraline is a naphthalenamine derivative which has the effect of selective serotonin reuptake inhibition. It has been used for major depression, and obsessive compulsive disorder. This study was performed to evaluate the pharmacokinetic (PK) characteristics after the administration of low dose sertraline for the purpose of exploring an application of microdosing methods in PK studies. METHODS An open-label, three-period, single-sequence, dose-escalation study was performed in 6 healthy Korean male volunteers. Subjects were administered a single dose of 5 mg, 25 mg and 50 mg sertraline orally in each period, with 1 week washouts between periods. Blood samples were obtained up to 96 h after drug administration. Plasma concentrations were determined using high performance liquid chromatography-tandem mass spectrometry. PK parameters of sertraline were analyzed using non-compartmental methods. RESULTS A total of 6 subjects completed the study. After the administration of sertraline at 5 mg, 25 mg and 50 mg, the median tmax were 6.0, 6.0 and 4.0 h and the mean (SD) elimination half-lives were 31.9 (6.5), 27.2 (6.7) and 28.0 (6.6) h, respectively. The AUC and Cmax increased dose-dependently. The dose-normalized mean (SD) AUC and Cmax were different in each dosing group (p < 0.01) with 2.0 (0.8), 5.3 (1.2) and 6.0 (1.9) mg × hr/l/mg in the 5 mg, 25 mg and 50 mg groups for dose-normalized AUC, and 0.07 (0.01), 0.18 (0.05) and 0.21 (0.08) mg/l/mg in the 5 mg, 25 mg and 50 mg groups for dose-normalized Cmax, respectively, which indicates a lack of dose proportionality. CONCLUSION A lack of dose proportional properties was shown in the 5 mg dose relative to the 25 mg and 50 mg doses of sertraline. This shows that the PK parameters for low-dose sertraline could be different from those in clinical concentrations. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|