Yasuhiro Tsuji

Population Pharmacokinetic Analysis of Everolimus Based on Albumin–Bilirubin Scores in Kidney Transplant Recipients

Toshinori Hirai, Takahiko Aoyama, Akiharu Okamoto, Chihiro Shiraishi et autres

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Differential salivary disposition of linezolid and its two major metabolites (PNU-142300 and PNU-142586) after a single dose in healthy adults

Yasuhiro Tsuji, Hitoshi Kawasuji, Tomona YAMADA, Fumihiro Kurosaki et autres

BACKGROUND: Salivary therapeutic drug monitoring of linezolid has been proposed as a non-invasive alternative to blood sampling for pharmacokinetic assessment. However, the salivary disposition and pharmacokinetics of the two major linezolid metabolites, PNU-142300 and PNU-142586, have not been characterized. OBJECTIVE: To evaluate …

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Population Pharmacokinetic Analysis and Modelling of Serum Uric Acid Dynamics in Patients Treated with Favipiravir

Tomona YAMADA, Hitoshi Kawasuji, Chika Ogami, Chihiro Hasegawa et autres

Background: Hyperuricemia is an adverse effect frequently observed during favipiravir treatment. The time course, from uric acid elevation to recovery, and quantitative relationship between drug exposure and changes in serum uric acid levels remain insufficiently characterized. We investigated the pharmacodynamic mechanism of …

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Enabling Technologies for Pharmacometrics Driven by Digital Twins in Clinical Research and Workforce Development

Yasuhiro Tsuji, Tomona YAMADA, Takahiko Aoyama

Digital twins, pharmacometrics, artificial intelligence, individualized pharmacotherapy, and workforce development are becoming increasingly interconnected in clinical pharmacy and drug development. Digital twin-driven pharmacometrics integrates mechanistic modeling with machine learning to enable patient-specific drug therapy prediction, simulation, and optimization. Recent applications include explainable …

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Risk prediction for linezolid-induced thrombocytopenia and exposure-guided safety optimization

Saki Takahashi, Yasuhiro Tsuji

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Leveraging ChatGPT for Vancomycin Therapeutic Drug Monitoring: Simulation Using Bayesian Estimation and Hyperparameter Optimization

Akira Kageyama, Takahiko Aoyama, Rikuya Maehara, Dai Harada et autres

The usefulness of ChatGPT, a large language model, has recently been explored in medical research. However, no studies have examined its reproducibility or applicability to therapeutic drug monitoring (TDM), a core task of clinical pharmacists. In this simulation study, we evaluated the …

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Simultaneous Determination of Linezolid, PNU-142300, and PNU-142586 in Human Serum via Ion-Pairing Reversed-Phase Liquid Chromatography with UV Detection

Fumihiro Kurosaki, Kanae SOMEYA, Tomona YAMADA, Naoki Oikawa et autres

In this study, we developed and validated a novel method of simultaneously measuring serum concentrations of linezolid (LZD) and its major metabolites, PNU-142300 and PNU-142586, in human serum using high-performance liquid chromatography coupled with an ultraviolet detector (HPLC-UV) for pharmacokinetic–pharmacodynamic analysis. LZD …

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[Open Superior Mesenteric Artery Bypass for Stanford Type A Acute Aortic Dissection with Mesenteric Malperfusion].

Takehiko Inoue, Akira Hashino, Yasuhiro Tsuji, Shinji Masuyama et autres

The optimal management of Stanford type A acute aortic dissection with mesenteric malperfusion(AMI)is controversial, Our strategy of AMI is open superior mesenteric artery(SMA)bypass prior to aortic repair, if we suspect AMI on computed tomography(CT)scan, whatever other findings might be or not, The …

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A Unified Approach to Synthesizing Four Linezolid Metabolites That May Cause Thrombocytopenia

Naoki Oikawa, Takumi Goto, Hiroaki Saito, Fumihiro Kurosaki et autres

Background/Objectives: Linezolid is a first-in-class oxazolidinone antibiotic that exhibits activity against Gram-positive pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. However, its clinical use is often restricted because of hematological toxicities, particularly thrombocytopenia, in patients with renal impairment. That side effect is …

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Generating and Modeling Virtual Patient Data from Published Population Pharmacokinetic Analyses: A Vancomycin Case Study

Hidefumi Kasai, Takahiko Aoyama, Yasuhiro Tsuji

Background/Objectives: In recent years, clinical pharmacometrics has become vital for drug development and clinical practice, particularly for predicting drug efficacy and safety. Population pharmacokinetic models are used for drugs for which therapeutic drug monitoring is recommended in clinical practice. Numerous population pharmacokinetic …

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High feasibility of salivary therapeutic drug monitoring in linezolid, but lower feasibility in tedizolid: a single-dose study in healthy subjects and a monocentric prospective exploratory study in patients who received linezolid

Hitoshi Kawasuji, Yasuhiro Tsuji, Keiko Miyaki, Takahiko Aoyama et autres

BACKGROUND: Salivary therapeutic drug monitoring (TDM) offers the potential to reduce the risks, burden, time and costs of blood-based TDM, but its feasibility for use with oxazolidinone antibiotics and the influence of food intake remain unknown. METHODS: We conducted a healthy subject …

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Pentazocine Pharmacodynamics in Children: Simulations to Assess Safety and Effectiveness

Takayuki Omori, Takahiko Aoyama, Yasuhiro Tsuji

BACKGROUND: Pentazocine is used for postoperative pain but is known to cause respiratory depression. Although hepatic metabolic activity in children gradually reaches adult levels, the effect of multiple doses in children with decreased clearance has not been elucidated. AIMS: The objective of …

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