[Evaluation of Prognostic Factors in Patients with Relapse and Unresectable Biliary Tract Cancer, Treated with S-1 after Failure of Gemcitabine].

Prognostic factors for patients with relapse and unresectable biliary tract cancer, treated with Tegafur Gimeracil Oteracil Potassium (S-1) after failure of gemcitabine (GEM), are unclear. We searched for prognostic factors in patients with relapse and unresectable biliary tract cancer treated with S-1 after failure of GEM, and investigated the relationship between prognostic factors, and the therapeutic effect of S-1. We retrospectively analyzed data of 33 patients with relapse and unresectable biliary tract cancer treated with S-1 after failure of GEM treatment. Statistically significant prognostic factors were extracted using Cox's proportional hazard model. Data was also collected on prognostic factors prior to the first dose of S-1, final prescription of S-1, and end of treatment. Changes in prognostic factors before the first dose of S-1, at final prescription of S-1, and at the end of treatment were evaluated using the Friedman test. Multivariate analysis identified neutrophil-lymphocyte ratio (NLR) [hazard ratio (HR)=4.599, p=0.004] and prognostic nutritional index (PNI) (HR=4.985, p=0.004) as independent poor prognostic factors for overall survival. Regarding the relationship between the therapeutic effect and prognostic factors, a significant change was observed in the change in PNI value from first administration of S-1 to the end of treatment (p=0.002). NLR and PNI are suggested to be prognostic factors in patients with relapse and unresectable biliary tract cancer, treated with S-1 after failure of GEM. Changes in PNI from the start of administration of S-1 may be related to therapeutic efficacy.

Application of a hemodialysis clearance prediction model using quantitative structure-pharmacokinetic relationship analysis.

Hemodialysis (HD) is a method used to remove biogenic substances or blood components that cause disease and some drugs used by patients to treat their diseases. Therefore, dosing schedule must be planned according to HD clearance (CLHD ) when medical treatment is provided to patients receiving HD. We aimed to clarify the physical properties (eg, octanol-water partition coefficient and molecular electronegativity) or pharmacokinetic parameters (eg, volume of distribution) of compounds affecting CLHD and to construct a mathematical model to predict CLHD . The analysis covered individual CLHD data for nine compounds from the literature. The molecular descriptors which are physical properties or pharmacokinetic parameters were calculated using the structural formula of each compound, and searched for factors related to CLHD among the calculated 148 molecular descriptors. Nonlinear mixed-effects model analysis with CLHD as objective variable and molecular descriptors as explanatory variable was conducted to examine the factor affecting CLHD and develop a model for predicting CLHD . The logarithm of the brain/blood partition coefficient was detected as a factor affecting CLHD . The predictive accuracy of CLHD using the constructed mathematical model with the logarithm of the brain/blood partition coefficient as explanatory variable was adequate.

Correlation between the Efficacy of Lamotrigine and the Serum Lamotrigine Level during the Remission Phase of Acute Bipolar II Depression: A Naturalistic and Unblinded Prospective Pilot Study.

Lamotrigine has acute antidepressant effects in patients with bipolar disorder. However, there is little information regarding appropriate serum levels of lamotrigine and the time until remission after the start of lamotrigine therapy in patients with bipolar II depression. This was a naturalistic and unblinded prospective pilot study. Twelve patients' depressive symptoms were evaluated using the Montgomery-Åsberg Depression Rating Scale (MADRS) at the start of treatment and at the time of remission, and blood samples were obtained at the time of remission. Mahalanobis distance was used to analyze the relationship between the MADRS improvement rate and the serum lamotrigine level. Furthermore, we calculated the Spearman's rank correlation coefficient for the relationship between the MADRS improvement rate and the serum lamotrigine level, and produced box plots of the serum lamotrigine level at remission and the time until remission. The Mahalanobis distance for the patient that was co-administered lamotrigine and valproic acid differed significantly from those of the other patients (p<0.001). There was no linear relationship between the serum lamotrigine level and the MADRS improvement rate among the patients that did not receive valproic acid. The median time from the start of lamotrigine therapy until remission was 6 weeks. The serum lamotrigine level does not have an important impact on the acute therapeutic effects of lamotrigine on bipolar II depression. In addition, we consider that different treatment options should be considered for non-responders who do not exhibit any improvement after the administration of lamotrigine for approximately 6 weeks.