Objective: To assess the pharmacokinetics including dose proportionality, safety, and tolerability of diazepam nasal spray (NRL-1) in Japanese participants, we conducted a phase 1 crossover study.

Methods: Japanese healthy male volunteers aged between 18 and 45 years were eligible for the study. Single doses of diazepam (5, 10, or 20 mg) were intranasally administered to participants in a randomly assigned order consisting of 6 treatment sequences. Treatment periods were separated by a minimum 28-day washout period.

Results: Between August 22, 2022 and November 29, 2022, 30 participants were enrolled into the study. Of these, 2 participants discontinued the study after receiving 5 and 20 mg of diazepam because of treatment emergent adverse events (TEAEs). All participants were included in the analysis. The median time to maximum plasma concentration of diazepam was 1.5 or 2.0 h at all dose levels, indicating rapid absorption. Increases in maximum observed plasma concentration and area under the plasma concentration-time curve for diazepam and its metabolite nordiazepam were almost linear over the dose range of 5 to 20 mg. The most common TEAE was somnolence followed by rhinalgia at all dose levels. Most of TEAEs were assessed as mild or moderate in severity. TEAEs leading to study discontinuation were depression and coronavirus disease 2019, which were considered unlikely or not related to the study drug.

Conclusions: Pharmacokinetic profiles of diazepam nasal spray in this study were similar to those obtained from the previous phase 1 studies conducted in Western countries. No safety concern specific to the Japanese population was observed.

Blood samples, which are typically obtained by venipuncture, are used for therapeutic drug monitoring (TDM). The “dry filter method” using filter paper, which is commonly used for newborn screening, is a convenient alternative to conventional methods for pharmacokinetic studies, TDM, and pharmacological research. This scoping review summarizes the current status, challenges, and perspectives of currently available filter paper methods and devices for whole blood, plasma, urine, breast milk, and saliva. Overall, 260 studies on filter paper microsampling for whole blood (review only), plasma, serum, urine, breast milk, and saliva (non-review) were retrieved from several literature databases and summarized. Although technical limitations have hindered the use of filter paper, particularly for blood samples, concerning home-based sample collection for clinical research, innovative developments in volume absorption microsampling and devices have provided alternatives to conventional methods. Urine, breast milk, and saliva were also used to evaluate various compounds and biological substances, but issues such as stability require further investigation. To apply the filter paper method in clinical research, a highly sensitive quantification system is essential; however, there are barriers to its introduction in laboratories. Furthermore, high-throughput and quality control from collection to measurement are necessary. To efficiently introduce microsampling methods using dry filter paper into clinical trials and research and maximize the utility of each biological sample, overcoming the existing challenges and reducing the burden on researchers, companies, and subjects are desired.

In medical institutions, there are few investigator sites that actually deliver investigational drugs to participants or investigator sites that establish procedures for such delivery. However, it is expected that medical institutions will need to prepare for the delivery of investigational drugs to participants' homes due to the rapid spread of emerging infectious diseases and disasters, as well as the international spread of decentralized clinical trials. This time, we created “Points to note when establishing procedures for delivering investigational drugs from medical institutions to participants” and “Flowchart for delivering investigational drugs from medical institutions to participants”. In the future, when creating “procedure manual for delivering investigational drugs from medical institutions to participants”, it will be necessary to consider whether “Points to note when establishing procedures for delivering investigational drugs from medical institutions to participants” and “Flowchart for delivering investigational drugs from medical institutions to participants” are useful. In addition, it is expected that, in the future, decentralized clinical trials will become more widespread internationally, and related regulations will be revised accordingly. Therefore, we would like to consider updating “Points to note when establishing procedures for delivering investigational drugs from medical institutions to participants” and “Flowchart for delivering investigational drugs from medical institutions to participants” in response to this.

Between November 2023 and January 2024, the supply of dacarbazine, an anticancer medication, was suspended. Suspension of cancer drug supplies can make it challenging to continue treatment, potentially having a significant impact on patient survival outcomes. This study aims to determine the impact of the dacarbazine supply suspension on clinical treatments, as well as the challenges associated with inter-institutional pharmaceutical borrowing. A survey conducted primarily among cancer treatment co-ordination hospitals in the Aichi Prefecture demonstrated that 55％ of them faced numerous treatment restrictions due to the supply suspension, such as interruptions in treatment, changes in treatment regimens, and reductions in dosages. Despite regulations under the Pharmaceutical and Medical Device Act, borrowing of pharmaceuticals between medical institutions has been identified as a beneficial solution for ongoing treatment, while also highlighting the associated challenges. These findings highlight the requirement for prompt information provision from pharmaceutical companies, strengthening co-operative systems between medical institutions, and flexible operation of the legal framework during emergencies as countermeasures to pharmaceutical supply suspensions. As a preventative measure against future similar supply issues, it is proposed that a collaborative system involving pharmaceutical companies, medical institutions, related academic societies, and the Ministry of Health, Labour, and Welfare maintain a pharmaceutical supply that does not disadvantage patients.