Efficacy of a melatonin receptor agonist and orexin receptor antagonists in preventing delirium symptoms in the olderly patients with stroke: a retrospective study.

Background: Post-stroke delirium affects between 24% and 43% of patients, and negatively impacts patient outcomes. Recently, research attention has been on preventive interventions for delirium, with melatonin receptor agonists and orexin receptor antagonists reported to be effective in preventing delirium in intensive care unit patients. However, the efficacy of these agents in preventing post-stroke delirium remain unclear.

Subjective symptoms are triggers for the detection of immune checkpoint inhibitor-induced interstitial lung disease and associate with disease severity: a single-center retrospective study.

Background: Interstitial lung disease (ILD) is one of the most common fatal immune-related adverse events (irAEs). ILD development adversely affects the continuation of anticancer drug therapy, including immune checkpoint inhibitor (ICI) therapy and prognosis. There are no established useful clinical indicators for the early detection of ILD.

Development of a 3-dimensional organotypic model with characteristics of peripheral sensory nerves.

We developed a rat dorsal root ganglion (DRG)-derived sensory nerve organotypic model by culturing DRG explants on an organoid culture device. With this method, a large number of organotypic cultures can be produced simultaneously with high reproducibility simply by seeding DRG explants derived from rat embryos. Unlike previous DRG explant models, this organotypic model consists of a ganglion and an axon bundle with myelinated A fibers, unmyelinated C fibers, and stereo-myelin-forming nodes of Ranvier.

Model-Informed Dosing Optimization of Tacrolimus for Concomitant Administration with Itraconazole to Japanese Lung Transplant Recipients.

Background: Tacrolimus is an immunosuppressant administered to patients undergoing lung transplantation. Itraconazole is often concomitantly used with tacrolimus to prevent fungal infections and increase tacrolimus concentration. However, the pharmacokinetics of tacrolimus in Japanese lung transplant recipients and the effect of itraconazole on its pharmacokinetics have not been adequately evaluated.

Association between Proton Pump Inhibitors, Immune Checkpoint Inhibitors, and Acute Kidney Injury: A Nested Case-Control Study.

Key Points: This is the first study to use a large database of patients with cancer to examine the association between the studied drugs and AKI. The use of either proton pump inhibitors or immune checkpoint inhibitors was associated with an increased risk of AKI. However, their additive interaction was not identified.

Influence of ensitrelvir or nirmatrelvir/ritonavir on tacrolimus clearance in kidney transplant recipients: a single-center case series.

Background: Among the oral antivirals used for treating patients with mild-to-moderate novel coronavirus disease 2019 (COVID-19), nirmatrelvir/ritonavir (NMV/RTV) and ensitrelvir (ESV) are inhibitors of cytochrome P450 (CYP) 3A, and therefore, can cause drug-drug interactions with concomitant medications. Tacrolimus (TAC), a substrate of CYP3A4/5, is administered for a long period to prevent rejection after kidney transplantation. TAC should be discontinued while using NMV/RTV because blood TAC levels significantly increase when these drugs are concomitantly administered.

A case of successful contribution of therapeutic drug monitoring of valganciclovir as the prophylaxis against cytomegalovirus infection in a lung transplant recipient.

Background: Ganciclovir and its prodrug, valganciclovir, are first-line agents for cytomegalovirus infection prophylaxis after lung transplantation. Although valganciclovir prophylaxis is known to result in severe leukopenia as an adverse effect, dosage adjustment based on therapeutic drug monitoring (TDM) of ganciclovir concentration is not generally implemented in clinical practice.

Case Presentation: In this report, we describe the case of a female in her fifties after lung transplantation who successfully maintained valganciclovir prophylaxis under TDM with a minimal occurrence of severe leukopenia.

Investigation of severe acute respiratory syndrome coronavirus 2 infection status in solid organ transplant recipients treated with tixagevimab/cilgavimab.

Introduction: Tixagevimab and cilgavimab (T/C) are neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be used to prevent SARS-CoV-2 infection in solid organ transplant (SOT) recipients. However, their neutralizing activity against recent variants was reduced, raising concerns regarding the emergence of breakthrough coronavirus diseases 2019 (COVID-19). This study aimed to investigate the status of the COVID-19 breakthrough after T/C administration.

Real-Time Particle Emission Monitoring for the Non-Invasive Prediction of Lung Deposition via a Dry Powder Inhaler.

Although inhalation therapy represents a promising drug delivery route for the treatment of respiratory diseases, the real-time evaluation of lung drug deposition remains an area yet to be fully explored. To evaluate the utility of the photo reflection method (PRM) as a real-time non-invasive monitoring of pulmonary drug delivery, the relationship between particle emission signals measured by the PRM and in vitro inhalation performance was evaluated in this study. Symbicort® Turbuhaler® was used as a model dry powder inhaler.

Potential treatment option of rivaroxaban for breastfeeding women: A case series.

The use of direct oral anticoagulants (DOACs) in breastfeeding women is currently challenging due to limited safety data for breastfeeding infants, and there have been no previous studies on the drug concentration in breastfeeding infants. We treated 2 patients (one case was twin pregnancy) with venous thromboembolisms in breastfeeding women administered rivaroxaban at our institution. Blood samples from the mothers and breastmilk samples were collected at time 0 and 2 h after the rivaroxaban administration, breastfeeding was conducted 2 h after the rivaroxaban administration, and blood samples from the infants were collected 2 h after breastfeeding (4 h after maternal rivaroxaban administration).

Comparison of safety and effectiveness between etanercept biosimilar LBEC0101 and reference in patients with rheumatoid arthritis in real-world data using the KURAMA cohort.

Objectives: Biosimilars are anticipated to be widely used in the treatment of rheumatoid arthritis (RA), owing to their cost efficiency; LBEC0101 was the first etanercept (ETN) biosimilar approved in Japan. However, there are limited real-world data comparing its safety and effectiveness with those of a reference product.

Methods: This study used data from the Kyoto University Rheumatoid Arthritis Management Alliance cohort, including patients with RA who received ETN therapy-ETN reference product (ETN-RP) or LBEC0101-between 2015 and 2021.

Development of extended pharmacokinetic models for propofol based on measured blood and brain concentrations.

Propofol's pharmacokinetics have been extensively studied using human blood samples and applied to target-controlled infusion systems; however, information on its concentration in the brain remains scarce. Therefore, this study aimed to simultaneously measure propofol plasma and brain concentrations in patients who underwent awake craniotomy and establish new pharmacokinetic model. Fifty-seven patients with brain tumors or brain lesions who underwent awake craniotomy were sequentially assigned to model-building and validating groups.

Low serum concentrations of bevacizumab and nivolumab owing to excessive urinary loss in patients with proteinuria: a case series.

Purpose: Proteinuria can cause interindividual variability in the pharmacokinetics of therapeutic antibodies and may affect therapeutic efficacy. Here, we measured the serum and urinary concentrations of bevacizumab (BV) and nivolumab (NIVO) in patients with proteinuria and reported a case series of these patients.

Methods: Thirty-two cancer patients who received BV every 3 weeks or NIVO every 2 weeks between November 2020 and September 2021 at Kyoto University Hospital were enrolled in this study.

[Management of high-alert medications by clinical pharmacological approaches].

During the past decade, many high-alert medications have been developed and used in clinical practice. Particularly, in the pharmacotherapy of high-alert medications with large individual differences, more attention is needed. To achieve appropriate and individualized pharmacotherapy, there are many issues to be addressed from a clinical pharmacology perspective, such as enhanced monitoring and prior risk identification.

Comparison of the safety and cost-effectiveness of nebulized liposomal amphotericin B and amphotericin B deoxycholate for antifungal prophylaxis after lung transplantation.

Introduction: Fungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs.

Relationships of Proton Pump Inhibitor-Induced Renal Injury with CYP2C19 Polymorphism: A Retrospective Cohort Study.

Proton pump inhibitors (PPIs) have recently been reported to be linked with nephrotoxicity. PPIs are metabolized mainly or partly by cytochrome P450 2C19 (CYP2C19). However, the relationship between CYP2C19 genetic polymorphism and PPI-induced nephrotoxicity is unclear.

Pharmacokinetics of GS-441524, the active metabolite of remdesivir, in patients receiving continuous renal replacement therapy: A case series.

Remdesivir plays a key role in the treatment of coronavirus disease in 2019 (COVID-19). Haemodialysis is sometimes required for hospitalised patients with COVID-19, and patients undergoing haemodialysis are at an increased risk of severe COVID-19. In the present study, we report the serum concentrations of GS-441524, the active metabolite of remdesivir, in four patients undergoing continuous renal replacement therapy (CRRT).

Trough ganciclovir concentration as predictor of leukopenia in lung transplant recipients receiving valganciclovir prophylaxis.

Background: Valganciclovir is the first-line agent for Cytomegalovirus prophylaxis after lung transplantation. However, its use is associated with a relatively high risk of hematological toxicity. This study aimed to investigate the relationship between trough ganciclovir concentration and hematologic toxicity in lung transplantation patients receiving valganciclovir prophylaxis, and identify factors that affect ganciclovir pharmacokinetics in this population.

Serum Concentrations of Infliximab and IL-6 for Predicting One-Year Discontinuation of Infliximab Treatment Owing to Secondary Non-response in Patients with Rheumatoid Arthritis.

Secondary non-response to infliximab (IFX) occurs in some patients with rheumatoid arthritis (RA). Although therapeutic drug monitoring (TDM) is a useful tool to optimize IFX therapy, it is unclear whether it can help to identify the risk of secondary non-response. This study aimed to explore the utility of serum levels of IFX or other biomarkers to predict IFX discontinuation owing to secondary non-response.

Decreased Analgesic Effect of Tramadol in Japanese Patients with CYP2D6 Intermediate Metabolizers after Orthopedic Surgery.

Tramadol is metabolized by CYP2D6 to an active metabolite, which in turn acts as an analgesic. This study aimed to investigate the impact of CYP2D6 genotype on the analgesic effect of tramadol in clinical practice. A retrospective cohort study was performed in patients treated with tramadol for postoperative pain after arthroscopic surgery for rotator cuff injury during April 2017-March 2019.

A case report of a prolonged decrease in tacrolimus clearance due to co-administration of nirmatrelvir/ritonavir in a lung transplant recipient receiving itraconazole prophylaxis.

Background: Drug-drug interaction management is complex. Nirmatrelvir/ritonavir is a potent cytochrome P450 (CYP) 3A inhibitor and influences pharmacokinetics of co-administered drugs. Although there are several reports about drug-drug interactions of nirmatrelvir/ritonavir, an influence of a concomitant use of nirmatrelvir/ritonavir and another potent CYP3A inhibitor on tacrolimus remains unclear.