|
KMID : 1038020150230020066
|
|
Translational and Clinical Pharmacology
2015 Volume.23 No. 2 p.66 ~ p.74
|
|
|
Population pharmacokinetic analysis of the multiple peaks phenomenon in sumatriptan
|
|
:Lee Joo-Mi
:Lim Mi-Sun/:Seong Sook-Jin/:Park Sung-Min/:Gwon Mi-Ri/:Han Seung-Hoon/:Lee Sung-Min/:Kim Woo-Mi/:Yoon Young-Ran/:Yoo Hee-Doo
|
|
|
Abstract
|
|
|
|
The objective of this study was to develop a population pharmacokinetic (PK) model for sumatriptan, which frequently shows an atypical absorption profile with multiple peaks. Sumatriptan, a selective agonist for the vascular serotonin (5-HT1) receptor that causes vasoconstriction of the cerebral arteries, is used for the acute treatment of migraine attack with or without aura. Despite its relatively high between-subject variability, few reports have addressed PK modeling of sumatriptan. Plasma data obtained after a single 50-mg oral dose of sumatriptan in 26 healthy Korean male subjects were used. Blood samples were collected 0 (predose), 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 12 h after dosing. Plasma sumatriptan concentrations were analyzed using UPLC/MS/MS. Population PK analysis was performed using plasma concentration data for sumatriptan with NONMEM (ver. 7.2). A total of 364 concentrations of sumatriptan were captured by a one-compartment model with first-order elimination, and a combined transit compartment model and first-order absorption with lag time was successful in describing the PK with multiple peaks in the absorption phase of sumatriptan. The creatinine clearance as a covariate significantly (P < 0.01) influenced the absorption fraction (f ). The final model was validated through a visual predictive check and bootstrapping with no serious model misspecification.
|
|
|
KEYWORD
|
|
|
Multiple peaks phenomenon, NONMEM, population pharmacokinetics, sumatriptan
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
 
|
|