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- 저자 : Palanichamy Ilankumaran (검색결과 1 건)
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박정신,한승훈,이종태,임동석,Palanichamy Ilankumaran,Jeffrey Meyer 대한임상약리학회 2014 Translational and Clinical Pharmacology Vol.22 No.2
SKL10406, triple monoamine reuptake inhibitor, is a novel antidepressant candidate. A PET studywas performed to investigate the occupancies of serotonin and dopamine transporters (SERT andDAT) in human brain, and the relationship between SKL10406 concentration and SERT occupancywas assessed using pharmacokinetic-pharmacodynamic (PK-PD) modeling methods. Fifteenhealthy volunteers were given SKL10406 100 mg/day for 6 days or 150 mg/day for 6 days after 100mg/day for 4 days. Each subject underwent full PK sampling for SKL10406 and PET scans at predose,4 h and 16 h after dosing at a steady state to investigate the occupancies of SERT and DAT using11C-DASB and 11C-PE2I, respectively. Naïve pooled method (NPM) and nonlinear mixed-effectmethods (ME) including a direct ME (DME) and an effect compartmental ME (EME) were used(NONMEM Ver. 7.2). Six and five subjects completed the studies for SERT and DAT, respectively. The final estimates of Emax (53.4%) and EC50 (11.8 ng/mL) from DME were relatively lower thanthose from NPM (Emax, 74.1%; EC50, 36.8 ng/mL) and EME (Emax, 68.6%; EC50, 40.2 ng/mL). DAToccupancy results were not modeled because of lower occupancies. The results showed that the dosageregimens may be applied in patient studies. However, difference between estimation methodsalerts that ME may not be a recommendable analysis tool for sparsely sampled PET scan data.
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