The pharmacokinetic parameters were estimated and the pharmacokinetic models of aprindine were evaluated in patients. Two pharmacokinetic models were used, comprising a linear elimination model and a non-linear elimination model, both one-compartment models in which first-order absorption is assumed. Twenty-two serum levels of patients in terms of TDM were measured and the pharmacokinetic parameters were estimated using the simple pool method. The pharmacokinetic parameters estimated using a linear model were ka= 0.244 (hr-1), ke=0.020 (hr-1) and Vd=1.778 (1/kg), while those using a non-linear model were ka=0.666 (hr-1), Km=2.022 (μg/ml), Vmax=0.106 (mg/hr/kg) and Vd=2.754 (1/kg).The non-linear model was more suitable than the linear model for the AIC (linear model:-12.59, non-linear model:-19.61). The parameters estimated using the non-linear model were therefore more accurate and were found to have a smaller bias than those estimated using the linear model.
The cover image is based on the Clinical Article Preoperative vascular mapping for anterolateral thigh flap surgeries: A clinical trial of photoacoustic tomography imaging by Itaru Tsuge MD, et al., https://doi.org/10.1002/micr.30531.
It was previously reported that free iron was released from rat red blood cells in both an in vitro study with a metabolite, mono-n-butylphthalate (MBP), of di-n-butylphthalate (DBP) and an in vivo study with oral DBP, inducing rat testicular atrophy in hypoxic conditions due to MBP-induced hemoglobin deprivation. This study investigated whether mono-n-alkylphthalates (alkyl-carbon C4-C6 ; MAP), which result in rat testicular damage, induce iron release from hemoglobin by incubation with rat red blood cells. Iron release was observed with C3-C6 MAP incubation at lower doses and with C1 and C2 MAP incubation at higher doses, but not with C7, C8, and C4(6) MAP.
Patient compliance is an important part of drug therapy, but not all patients take their medication exactly as directed. Although it is very important to investigate and identify factors that contribute to poor compliance, there have so far been very few studies of this kind in Japan. We therefore performed a cross-sectional study to analyze the factors associated with poor patient compliance (various patient background factors and a dozen matters dealing with medical care: the relationship between physicians and hospital staff, the time required to visit hospital, the drug therapy regimen, etc.) using the data obtained from patients who had been subjects of a QOL study on Carvedilol.The results showed that patient compliance was “good” is 83.3% of the patients, and that compliance was poorer among the following three groups of patients: employed patients (odds ratio: 5.15, 95% confidence level: 1.53-17.30, p=0.01), female patients (odds ratio: 3.39, 95% confidence level: 1.07-10.74, p=0.038), and patients who felt that their attending physicians did not provide enough information about the administered drug (odds ratio: 2.58, 95% confidence level: 0.88-7.58, p=0.084).
Abstract Mesenchymal transition is common to many aggressive cancers including breast, glioblastoma (GBM), lung and pancreatic cancers characterized by chemo/radiotherapy-resistance and cancer stem cell-like property. Claudin-low msenchymal subtype in triple-negative breast cancer (TNBC) is a major problem due to the lack of molecularly-targeting drugs. So far, we have identified an shRNA (shP1) which can induce mesenchymal to epithelial transition (MET) in shRNA library screening using positive selection reporter system in MDA-MB-231 mesenchymal TNBC cell line. Here, we have analyzed the effect of shP1 on morphology, transcription and cell proliferation in various mesenchymal cancer cell lines derived from breast, glioblastoma (GBM), lung and pancreatic cancers. The shP1 increased E-cadherin promoter-driven GFP in a wide range of mesenchymal cancers including brain, breast, pancreatic, lung origin. Drastic morphology change introduced by shP1 was observed both in 2D and 3D cultures (matrigel, collagen), reducing their invasive and branching morphogenesis, especially in U251 GBM and MDA-MB-231 TNBC cell lines. The shP1-introduced cells are more sensitive to EGFR-inhibition and paclitaxel in TNBC cell line, reminiscent of reversal of therapy-resistant phenotype. Gene expression analysis reveals alteration of pathways related to cell adhesion, ERRB signal pathway, apoptosis and cytokines signaling. Of note, shP1-introduced U251 cells increased gene expression characteristic of proneural subtype, indicating shP1 reverted the subtype from mesenchymal to proneural. These results suggest that although U251 and MDA-MB-231 cell lines are of different tissue origins, their mesenchymal property can be reverted by the same program targeted by single shRNA. These results provide a rationale of MET as therapeutic for a wide range of cancers with mesenchymal property. Citation Format: Kiyotsugu Yoshikawa, Hiroaki Sakai, Masahiro Shimazaki, Nobuhiro Okada, Yoshiaki Matsumoto, Ellis Reinherz, Masakazu Toi. Reversal of mesenchymal phenotype of triple-negative breast cancer and glioblastoma cells and its therapeutic implication. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr C20.
The pharmacokinetic parameters of the intravenous anesthetic drug propofol were investigated. Propofol was administered using an infusion pump at variable rates (10, 8, 6 and 4 mg/kg/hr) to 15 Japanese patients undergoing surgery, as part of a protocol for the induction of general anesthesia that included the use of nitrous oxide and muscle relaxants. The weight of the patients was 56±10 kg (mean±SD). The blood propofol concentrations were determined using high performance liquid chromatography and ECD detection. Blood propofol concentrations were also measured when the patients awoke. The blood propofol concentrations were fitted by a three-compartment model using the maximum likelihood estimation. Bias, accuracy and precision between the measured and the predicted blood concentrations were calculated using the pharmacokinetic parameters obtained.The obtained elimination clearance (CL), of 49 ml/kg/min, was greater than that reported in a different propofol study in which the weight of the patients was 71±17 kg. The blood propofol concentration when the patients opened their eyes in response to a verbal command was 793.0±67 ng/ml (mean±SD). The prediction error calculated from our parameters (mean absolute error, 0.12, root mean squared error, 0.078), particularly that at awakening, was significantly smaller than that calculated from parameters obtained in a previous report. The pharmacokinetic parameters in this study were useful for the prediction of the propofol blood concentration, as was the application of a computer controlled infusion pump technique.
The dissolution behavior of the aspirin enteric granule prepared using acylglycerols, glyceryl monostearate (GMS) and glyceryl trilaurate (GTL), was investigated in vitro and in human subjects in a fasting or non-fasting state. Aspirin was slowly released from the granule in vitro at pH 1.2. No acceleration of the aspirin dissolution rate in the medium without lipase and cholic acid was observed when the pH level of the medium increased to a neutral region (pH 6.4). However, the dissolution of aspirin was significantly increased by increasing the concentrations of lipase and cholic acid in the medium. Lipase appears to play an essential role in the dissolution process of aspirin granules. In human subjects, the average levels of the cumulative amount of total salicylate excreted in a urine-time curve, and the mean residence time (MRT) obtained after oral administration of a granule in the fasting state were markedly delayed in comparison with the results observed using and aqueous solution and a crystalline form of aspirin. In comparing the fasting condition with the non-fasting condtion (after food ingestion), no significant difference was recognized in the total amount of salicylate excreted in urine to an infinite time (Ae(∞)), whether the MRT was obtained by granule, crystalline form or aqueous solution. It can be concluded that aspirin granule prepared by GMS and GTL has a property of pancreatic lipase-sensitive dissolution, and its bioavailability is unaffected by food intake.
