Background: Rifampin exhibits highly variable exposure in tuberculosis patients, leading to adverse effects or treatment failure.This study aimed to develop therapeutic drug monitoring (TDM) strategy for rifampin using a single concentration-time point to estimate the area under the concentration-time curve (AUC), with the potential to reduce the number of blood draws. Methods: Plasma concentration(Cp)-time data were obtained from tuberculosis patients by collecting serial venous blood samples after rifampin administration. The Cp timepoint (Ct ) that predicts AUC best was explored using linear regression (Exploration). The accuracy and precision were evaluated using Bland-Altman plot. Physiologically based pharmacokinetic modeling approach was used to evaluate whether the single C t point identified in Exploration provides the best prediction of the AUC (Complement). Results: Cp-time data obtained from 26 participants were evaluable for the determination of AUC by Ct . In Exploration, C4 best predicted the AUC (r2 =0.91, p<0.0001), followed by C2 (r2 =0.84, p<0.0001). In AUC prediction by C4 , the datapoints for predict-ed and observed AUC pairs were randomly scattered in Bland-Altman plot with the mean bias of −0.029 μg · h/mL, and the 95% limit of agreement of −21.1 to 21.1 μg · h/mL. In Complement, C4,sim best predicted the AUC (r2 =0.86, p<0.0001), which supports that C4 reliably predicted AUC. Conclusions For improving treatment outcomes in the treatment of tuberculosis, a single concentration monitoring is applicable to rifampin TDM instead of AUC, potentially making the process less invasive, painful and cumbersome for patients, clinicians and healthcare providers.

Reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2 ), are critical mediators of oxidative stress, which can lead to cellular damage and contribute to various kidney diseases. Poria cocos, a traditional medicinal fungus, has demonstrated various health benefits, particularly in gastrointestinal and neurological health. This study investigates the potential of P. cocos extract (PCE) to reduce H2O2 -induced oxidative injury and promote cell proliferation in feline kidney epithelial cells. PCE treatment significantly improved cell viability in H2O2 -injured cells in a dose-dependent manner. PCE reduced intracellular ROS levels, including superoxide anions, hydroxyl radicals, and intracellular H2O2 , while enhancing the activities of antioxidant enzymes such as superoxide dismutase and catalase. Furthermore, PCE treatment promoted cell proliferation, as evidenced by increased Ki-67 expression, and enhanced the phosphorylation of ERK1/2 and AKT, which are key mediators of cell survival and proliferation. PCE effectively mitigates oxidative stress and promotes cell proliferation in kidney epithelial cells through the activation of the ERK1/2 and AKT pathways, suggesting its potential as a therapeutic agent for oxidative stress-related kidney diseases.

Background: Regulatory agencies operate their own advisory committee with external experts to address complex scientific issues in the approval of pharmaceutical products. However, each advisory committee operates very differently. Hence, the authors per-formed a comprehensive gap analysis among the committees operated by Food and Drug Administration (FDA), European Medicines Agency (EMA) and Ministry of Food and Drug Safety (MFDS). Methods: The regulations, guidelines, minutes and reports on advisory committees were retrieved from the websites of FDA, EMA and MFDS. A gap analysis comparing the advisory committeesof each regulatory authority was performed, including the disclosure of information and meeting procedures, and conflict-of-interest policies. Results: Substantial differences were found among the advisory committees in the strictness of conflict-of-interests and the transparency of meeting details. Whereas FDA and EMA disclose the detailed curriculum vitae of each committee member, MFDS does only names and majors. Whereas FDA live-streams each meeting and publishes the transcript of all dialogues by each member, EMA and MFDS release only anonymized summary minutes without live broadcasts. Whereas FDA and EMA require members to disclose their financial interests, MFDS merely requires signing a statement that confirms no conflict-of-interest. Conclusions Compared with Advisory Committee of FDA and Scientific Committee of EMA, the Central Pharmaceutical Affairs Advisory Committee (CPAAC) of MFDS appears to require substantial improvements in the disclosure of conflict-of-interests and the transparency ofmeeting details. This gap analysis will likely serve as a basis for policy discussions to improve the credibility of CPAAC.

Background: Hematocrit is usually measured from venous blood collected by invasive venipuncture. This study was performed to determine hematocrit accurately and precisely using minimally invasive volumetric absorptive microsampling (VAMS) technique.Such technique is to be applied to determining hematocrit in various clinical settings for the care, including therapeutic drug monitoring, of neonatal or epileptic patients, or patients with high risk of infection or bleeding. Methods: The study was performed using 31 VAMS samples obtained from 21 pancreatic cancer patients. Hematocrit was determined using the values of potassium concentrations obtained from blood in VAMS tips (HctVAMS ). HctVAMS was compared with hematocrit measured from blood collected by venipuncture (HctVP ). The accuracy and precision of HctVAMS in comparison to HctVP were evaluated using BlandAltman plot, Deming regression and mountain plot. Results: Bland-Altman plot displayed a random scattering pattern of the differences between HctVAMS and HctVP with the mean bias of −0.010 and the 95% limit of agreement ranging from −0.063 to 0.044.Deming regression for HctVAMS and HctVP line demonstrated very small proportional and constant biases of 1.04 and −0.003, respectively. Mountain plot exhibited a narrow and symmetrical distribution of the differences with their median of −0.011 and central 95% range from −0.049 to 0.033. Conclusion Hematocrit was accurately and precisely determined using less invasive VAMS technique. Such technique appears to be applicable to determining hematocrit in situations that venipuncture is not favorable or possible.