+The first two authors contributed equally to this work.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 NON-MEM (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.

We developed an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of acetaminophen concentration in human plasma. Following protein precipitated extraction, the analytes were separated and analyzed using an UPLC-MS/MS in the multiple reaction monitoring (MRM) mode with the respective [M+H] + ions, m/z 152.06 → 110.16 for acetaminophen and m/z 180.18 → 138.12 for phenacetin (internal standard, IS). The method showed a linear response from 1 to 100 µg/mL (r > 0.9982). The limit of quantitation for acetaminophen in plasma was 1 µg/mL. The intra-and inter-day accuracy ranged in the ranges of 94.40-99.56% and 90.00-99.20%, respectively. The intra-and inter-day precision ranged in the ranges of 2.64-10.76% and 6.84-15.83%, respectively. This method was simple, reliable, precise and accurate and can be used to determine the concentration of acetaminophen in human plasma. Finally, this fully validated method was successfully applied to a pharmacokinetic study of acetaminophen in healthy volunteers following oral administration. Methods Chemical and reagents Acetaminophen and phenacetin (internal standard, IS) were

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Backgrounds/Aims: Pancreatic cancer (PC) patients have poor prognoses because this cancer is typically diagnosed at an advanced stage and the therapeutic options are limited. We examined the potential of metabolic profiling for early diagnosis and identification of potential therapeutic targets. Methods: Ten patients and 10 healthy volunteer controls older than 20 years of age were enrolled between May and December 2015. The patients were confirmed to have pancreatic ductal adenocarcinoma cytologically or histologically. Blood plasma samples were derivatized and analyzed by gas chromatography mass spectrometry (GC-MS). Untargeted GC-MS data were analyzed using statistical methods, including Wilcoxon rank-sum test and principal component analyses. Results: L-lysine was 1.36-fold higher in patients than in healthy controls (p<0.05). L-leucine was 0.63-fold lower (p<0.01) and palmitic acid was 0.93-fold lower (p<0.5) in patients than in controls. Orthogonal partial least squared-discriminant analysis revealed significant differences between the patients and controls. Conclusions:This study suggests that the metabolic profiles of patients with PC are distinct from those of the healthy population. Further studies are required to develop methods for early diagnosis and identify therapeutic targets. Korean J Pancreas Biliary Tract 2019;24(2):61-67