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Background This study evaluated the prognostic value of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) together with host-related factors in patients with unresectable advanced gastric cancer. Methods The study enrolled 262 patients who received chemotherapy for unresectable advanced gastric cancer at Kochi Medical School from 2007 to 2015. Clinicopathological information and systemic inflammatory response data were analyzed for associations between baseline cancer-related prognostic variables and survival outcomes. Results The median survival time was significantly lower for patients with high ALP, high LDH, high total bilirubin, high aspartate aminotransferase, high alanine transaminase, high gamma-glutamyltransferase, high creatinine, a Glasgow prognostic score (GPS) of 1 or 2 score compared to GPS 0, higher compared to lower neutrophil to lymphocyte ratio (NLR) 3.9, lower compared to higher prognostic nutrition index 36.1, T3-4 compared to T1-2 tumor and diffuse-type compared to intestinaltype histology. Multivariate survival analysis identified high ALP 322 (HR 1.808; 95% CI 1.015-3.220; P = 0.044), T2-3 (HR 2.622; 95% CI 1.224-5.618; P = 0.013), and diffuse-type gastric cancer (HR 2.325; 95% CI 1.341-4.032; P = 0.003) as significant independent predictors of worse prognosis in the studied group of cancer patients. Conclusions High level of ALP is an independent, worse prognosis factor for patients receiving chemotherapy for unresectable and recurrent gastric cancer.

ABSTRACT:The pharmacokinetics of daikenchuto (TJ-100), a pharmaceuticalgrade traditional Japanese medicine, were investigated in healthy Japanese volunteers after a single oral administration of 2.5-, 5-, and 10-g doses. Six ingredients [hydroxy-␣-sanshool (HAS), hydroxy-␤-sanshool (HBS), [6]-shogaol (6S), [10]-shogaol (10S), ginsenoside Rb 1 (GRB1), and ginsenoside Rg 1 (GRG1)] of TJ-100 were determined by using liquid chromatography-tandem mass spectrometry. The results indicated that HAS, an ingredient derived from Zanthoxylum piperitum fruit, exhibited the highest plasma concentration among the six ingredients investigated. The plasma concentrations of HAS, HBS, 6S, and 10S reached the maximum concentration (approximately 400, 80, 0.14, and 0.6 ng/ml, respectively, after a 5-g administration of TJ-100) within 30 min after administration, and the mean half-life was approximately 2 h. Thus, these compounds were rapidly absorbed and eliminated. The plasma concentration of GRB1 reached the maximum concentration (2 ng/ml after a 5-g administration of TJ-100) at approximately 4 h after administration and the half-life of GRB1 was approximately 40 h. The plasma concentration of GRG1 was extremely low (<0.023 ng/ml). The pharmacokinetics of HAS, HBS, 6S, and 10S, were linear within the range of 2.5 to 10 g/day of TJ-100. On the other hand, the kinetics of GRB1 and GRG1 were not proportional to dosage, and plateauing was observed.

BackgroundRikkunshito, a traditional Japanese (Kampo) medicine, has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux. This study investigated the exposure and pharmacokinetics of the ingredients of rikkunshito in healthy volunteers.Methods and ResultsFirst, an exploratory nonrandomized, open-label, one-period, noncrossover study using four healthy Japanese volunteers to detect 32 typical ingredients of rikkunshito in plasma and urine. As a result, 18 or 21 of 32 ingredients was detected in plasma or urine samples after oral administration of rikkunshito (7.5 g/day). Furthermore, a randomized, open-label, three-arm, three-period, crossover study using 21 subjects was conducted to determine the amounts of exposure and pharmacokinetic parameters of nine ingredients derived from rikkunshito (atractylodin, atractylodin carboxylic acid, pachymic acid, 3,3′,4′,5,6,7,8-heptamethoxyflavone, naringenin, nobiletin, liquiritigenin, isoliquiritigenin, and 18β-glycyrrhetinic acid) after oral administration of rikkunshito at three different doses (2.5, 5.0, or 7.5 g/day) during each period. The pharmacokinetic profiles of the nine ingredients in plasma were characterized. The geometric means (95% confidence interval) for the Cmax of the ingredients at a dose of 7.5 g were 1570 (1210–2040), 14,300 (12,200–16,800), 91.0 (71.8–115), 105 (75.6–144), 1150 (802–1650), 35.9 (24.6–52.5), 800 (672–952), 42.8 (30.4–60.3), and 55,600 (39,600–78,100) pg/mL, respectively, and for the AUC0–last were 1760 (1290–2390), 12700 (11,100–14,600), 1210 (882–1650), 225 (157–322), 4630 (2930–7320), 35.7 (20.4–62.7), 4040 (3260–5010), 122 (88.2–168), and 832,000 (628,000–1,100,000) pg·h/mL respectively.ConclusionsWe identified the ingredients of rikkunshito that are absorbed in humans. Furthermore, we determined the pharmacokinetics of nine ingredients derived from rikkunshito. This information will be useful for elucidating the pharmacological effects of rikkunshito.Trial RegistrationJapan Pharmaceutical Information Center #CTI-121801 and -142522

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