ered in clinical practice. The contribution ratios (CR) of metabolic enzymes to the systemic clearance of a drug can be estimated from in vitro studies. https://www.selleckchem.com/products/pyrotinib.html Another feasible approach is to calculate them based on the increase in the area under the time-concentration curve (AUC) caused by the co-administration of a potent and selective inhibitor in a clinical drug-drug interaction (DDI) study. However, some factors, such as the inhibitory potency of the inhibitor and the inhibition of first-pass metabolism, might affect the estimation of CR based on clinical DDI studies. We aimed to validate the accuracy of the DDI-based estimation of CR using an in silico approach. An in silico DDI study was conducted using a population-based physiological pharmacokinetic simulator to estimate the CR of cytochrome P450 (CYP)3A4 for zolpidem, sildenafil, omeprazole, triazolam, and repaglinide. The ratio of the AUC value seen in the presence of an inhibitor (ketoconazole or itraconazole) to that observed in the absence of the inhibitor (AUC ratio) was also calculated. The CR for CYP3A4 obtained using the simulator (CR ) were compared with those calculated from the AUC ratio (CR ). When ketoconazole was used, good correlations between the CR and CR were obtained for all examined substrates (inconsistencies were seen in < 10% of subjects). CR estimates derived from the AUC ratio were found to be accurate. Some underestimation was observed, possibly due to incomplete inhibition, and some overestimation caused by extensive first-pass metabolism was noted. This study verified that CR obtained from AUC ratios in DDI studies are quite reliable. This study verified that CR obtained from AUC ratios in DDI studies are quite reliable. This study aimed to compare the rate of hypoglycemic events from all spontaneously reported adverse events (AEs) between insulin detemir and insulin degludec using the Korea Adverse Event Reporting System (KAERS) database. We analyzed data on the reported hypoglycemia events retrieved from adverse drug reactions (ADR) on the use of different insulin types from 2016 to 2017 in the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD). After defining hypoglycemic events as the AE of interest, we performed a disproportionality analysis by calculating the reporting odds ratio (ROR) to identify the disproportionality of AEs following treatment with insulin degludec (IDeg) and insulin detemir (IDet). Because spontaneously reported hypoglycemic events were not distinguished between insulin glargine 100U/mL (Gla-100) and insulin glargine 300U/mL (Gla-300) due to same ATC code by KIDS-KD, direct comparisons of Gla-100 and Gla-300 or comparisons of each analog ugh disproportionality analysis using the spontaneous ADR reporting system, IDeg showed a relatively lower rate of reported hypoglycemic events than IDet. This study aimed to describe the area under the plasma concentration-time curve (AUC) and the relationship with hematological toxicity plus clinical responses of docetaxel in patients with nasopharyngeal carcinoma. Furthermore, a suitable docetaxel exposure level would be identified to guide clinical dosing. 96 patients with locally advanced or metastatic nasopharyngeal carcinoma treated with docetaxel-based chemotherapy were enrolled. Docetaxel was measured by turbidimetric immunoassay. Associations between docetaxel exposure and hematologic toxicity, effect, and recurrence time were analyzed. Receiver operating characteristic curve analysis was performed to determine an optimal AUC value to predict the decrease in absolute neutrophil counts. Interpatient variability was large with regard to exposure (AUC) and clearance. The AUC values of 76 patients in course 1 varied more than 4 fold (3.17±0.84 µg×h/mL, ranging from 1.4 to 6.0 µg×h/mL). Clearance was 42.8L/h (ranging from 20.8 to 73.7L/h) with ~3-fold interindividual variability. The incidence of grade 3/4 leukopenia, 3/4 neutropenia, and febrile neutropenia was 46.3, 85.2, and 13.5%, respectively, in course 1. Docetaxel exposure was the only significant predictor (p<0.001) of severe toxicity, including grade 4 neutropenia and febrile neutropenia. A cutoff value of 2.85 µg×h/mL was selected as the target AUC. Higher AUC values were not observed to be associated with better drug effect. The dose was calculated based on individual clearance and a target AUC of 2.85 µg×h/mL, helping to adjust the next cycle of doses and solve interpatient variability. The dose was calculated based on individual clearance and a target AUC of 2.85 µg×h/mL, helping to adjust the next cycle of doses and solve interpatient variability. Limited evidence is available regarding the effectiveness of a specialized continuous renal replacement therapy (CRRT) team approach. Hence, we aimed to evaluate the effectiveness of a specialized CRRT team intervention in a Japanese hospital. We retrospectively identified adult patients who underwent CRRT in the intensive care unit (ICU) from July 2015 to June 2019 and divided them into two groups based on whether or not they received CRRT team intervention. We extracted data from the electronic medical record database. The concurrent effects of various factors on study outcomes were analyzed by multivariate analysis using a generalized linear model. A total of 540 patients were included. Baseline characteristics were similar in the two groups. In univariate analysis, no significant differences were found in in-hospital mortality (34.0 vs. 30.8%; risk difference, -3.2%; 95% confidence interval, -12.6 to 6.1), total duration of ICU stay, total CRRT time, and the proportion of patients starting maintenance hemodialysis during hospitalization between both groups. Multivariate analysis also indicated no significant differences. In this study, no significant difference was found in patient outcomes between both groups. The results suggest that the CRRT team should have integrated protocols and play a core role in CRRT management. In this study, no significant difference was found in patient outcomes between both groups. The results suggest that the CRRT team should have integrated protocols and play a core role in CRRT management.