Absorption, metabolism, and excretion of oral [C] radiolabeled donafenib: an open-label, phase I, single-dose study in humans.

Purpose: The study aims to investigate the absorption, metabolism, and excretion of donafenib, a deuterated derivative of sorafenib, in healthy Chinese male volunteers.

Methods: Six healthy Chinese male volunteers were administered a single oral dose of 300 mg donafenib containing 120 µCi of [14 C]-donafenib. The study involved collecting and analyzing plasma, urine, and feces samples to determine the recovery and distribution of total radioactivity, identify metabolites, and assess the metabolic pathways of donafenib.

Human dose-escalation study of PET imaging CD8 T-cell infiltration in solid malignancies with [Ga]Ga -NODAGA-SNA006.

Purpose: A noninvasive method for evaluating the infiltration of CD8 T cells in tumors is urgently needed to monitor the response to immunotherapy. This study investigated the performance of a [Ga]Ga-NODAGA-SNA006 in positron emission tomography (PET) imaging of CD8 T cells in patients with solid malignancies.

Methods: This human dose-escalation PET imaging study involved eleven patients (lung cancer, 8; gastric carcinoma, 1; esophageal carcinoma, 2).

Clinical pharmacokinetic characteristics of Jaktinib in subjects with hepatic impairment in a phase I trial.

Jaktinib is a novel Janus kinase (JAK) inhibitor, and a phase I clinical trial of single-dose Jaktinib was conducted in a population of subjects with hepatic impairment to assess the safety, tolerability, and pharmacokinetic characteristics of Jaktinib. The patients were administered orally with 100 mg Jaktinib on day 1 in all the mild hepatic impairment group (mild group, n = 8), moderate hepatic impairment group (moderate group, n = 8) and normal hepatic function group (normal group, n = 8), and the blood samples were collected for later analysis. The mild to moderate hepatic impairment affected the metabolism of Jaktinib, which may lead to accumulation of original Jaktinib.

Development of a Specifically Labeled Zr Antibody for the Noninvasive Imaging of Tumors Overexpressing B7-H3.

B7-H3 has emerged as a promising target and potential biomarker for diagnosing tumors, evaluating treatment efficacy, and determining patient prognosis. Hu4G4 is a recombinant humanized antibody that selectively targets the extracellular domain of human B7-H3. In this study, we describe the radiolabeling of hu4G4 with the positron emission tomography (PET) emitter radionuclide zirconium 89 (Zr) and evaluate its potency as an immuno-PET tracer for B7-H3-targeted imaging by comparing it and to [Zr]Zr-DFO-DS-5573a using various models.

Optimising infliximab induction dosing to achieve clinical remission in Chinese patients with Crohn's disease.

Aims: A strategy based on therapeutic drug monitoring and population pharmacokinetic (popPK) models would likely increase the rate of clinical remission (CR) after infliximab (IFX) induction in patients with Crohn's disease (CD). This study aimed to evaluate the relationship between early IFX levels and antibodies to infliximab (ATI) and CR at week 14 and simulate the probability of attaining the identified exposure target.

Methods: Patients with CD (n = 140) treated with IFX were enrolled to develop the popPK model.

Pharmacokinetics, Mass Balance, and Biotransformation of [C]tinengotinib, A Novel Multi-target Kinase Inhibitor, in Healthy Subjects.

Background And Objective: Tinengotinib, a novel multi-target small molecule kinase inhibitor, is currently undergoing phase II clinical trial in the USA and China. The purpose of this open-label study was to investigate the absorption, metabolism, and excretion of [C]tinengotinib following a single oral dose in healthy subjects.

Methods: Six healthy male subjects received a single oral dose of [C]tinengotinib capsules at 10 mg/100 µCi, and blood, urine, and feces samples were collected.

Evidence-based expert consensus on clinical management of safety of Bruton's tyrosine kinase inhibitors (2024).

Bruton's tyrosine kinase inhibitors (BTKis) have revolutionized the treatment of B-cell lymphomas. However, safety issues related to the use of BTKis may hinder treatment continuity and further affect clinical efficacy. A comprehensive and systematic expert consensus from a pharmacological perspective is lacking for safety issues associated with BTKi treatment.

Machine learning guided prediction of warfarin blood levels for personalized medicine based on clinical longitudinal data from cardiac surgery patients: a prospective observational study.

Background: Warfarin is a common oral anticoagulant, and its effects vary widely among individuals. Numerous dose-prediction algorithms have been reported based on cross-sectional data generated via multiple linear regression or machine learning. This study aimed to construct an information fusion perturbation theory and machine-learning prediction model of warfarin blood levels based on clinical longitudinal data from cardiac surgery patients.

Biotransformation and disposition characteristics of HSK7653, a novel long-acting dipeptidyl peptidase-4 inhibitor for the treatment of type 2 diabetes.

Aim: To investigate the metabolism and disposition characteristics of HSK7653 in healthy male Chinese participants.

Methods: A single oral dose of 80 μCi (25 mg) [C]HSK7653 capsules was administered to six healthy participants, and blood, plasma, urine and faeces were collected. Quantitative and qualitative analysis was conducted to investigate the pharmacokinetics, blood-to-plasma ratio, mass balance and metabolism of HSK7653.

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Tolerability After Subcutaneous Administration of Tozorakimab in Healthy Chinese Participants.

Tozorakimab is a high-affinity human immunoglobulin G1 monoclonal antibody that neutralizes interleukin (IL)-33, an IL-1 family cytokine. This phase 1, single-center, randomized, double-blind, placebo-controlled, single ascending dose study (NCT05070312) evaluated tozorakimab in a healthy Chinese population. Outcomes included the characterization of the pharmacokinetic (PK) profile and immunogenicity of tozorakimab.

Pharmacokinetics, mass balance, and metabolism of [C]envonalkib (TQ-B3139), a novel ALK tyrosine kinase inhibitor, in healthy Chinese subjects.

Purpose: Envonalkib (TQ-B3139) is a novel, potent anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor used to treat ALK-positive non-small cell lung cancer. This phase I mass balance study investigated the pharmacokinetics, metabolism, and excretion of C-radiolabeled envonalkib in healthy Chinese male subjects.

Methods: A single oral dose of 600 mg (150 µCi) [C]envonalkib was administered to healthy male subjects under fasted state.

Warfarin-A natural anticoagulant: A review of research trends for precision medication.

Background: Warfarin is a widely prescribed anticoagulant in the clinic. It has a more considerable individual variability, and many factors affect its variability. Mathematical models can quantify the quantitative impact of these factors on individual variability.

A Phase I Clinical Study of the Pharmacokinetics and Safety of Prusogliptin Tablets in Subjects with Mild to Moderate Hepatic Insufficiency and Normal Liver Function.

Background: Prusogliptin is a potent and selective DPP-4 inhibitor. In different animal models, Prusogliptin showed potential efficacy in the treatment of type 2 diabetes. However, the knowledge of its pharmacokinetics and safety in patients with liver dysfunction is limited.

A Randomized Trial Comparing Standard of Care to Bayesian Warfarin Dose Individualization.

The quality of warfarin treatment may be improved if management is guided by the use of models based upon pharmacokinetic-pharmacodynamic theory. A prospective, two-armed, single-blind, randomized controlled trial compared management aided by a web-based dose calculator (NextDose) with standard clinical care. Participants were 240 adults receiving warfarin therapy following cardiac surgery, followed up until the first outpatient appointment at least 3 months after warfarin initiation.

The reference range of lamotrigine in the treatment of epilepsy in children: a systematic review.

Purpose: This study intends to assess the reference range of lamotrigine concentration for treating childhood epilepsy.

Methods: PubMed, Ovid-Embase, The Cochrane Library, CNKI, WanFang data and VIP databases were searched from database inception to January 2022. RCT, cohort study, case-control study, cross-sectional study that estimated the reference range of lamotrigine for children epilepsy treatment were included.

Assessment of risk factors for acute graft--host disease post-hematopoietic stem cell transplantation: a retrospective study based on a proportional odds model using a nonlinear mixed-effects model.

Background: Acute graft--host disease (aGVHD) is a major complication following hematopoietic stem cell transplantation (HSCT).

Objective: This study aimed to explore the risk factors for the incidence of aGVHD in patients post-HSCT.

Design: This was a retrospective study.

Pharmacokinetics, Mass Balance and Metabolism of [C]HSK21542, a Novel Kappa Opioid Receptor Agonist, in Humans.

Background And Objective: HSK21542, a synthetic short-chain polypeptide, is a selective peripheral kappa opioid receptor (KOR) agonist. In this single-centre, non-randomized, open-label study, the pharmacokinetics, mass balance, metabolism and excretion of HSK21542 were investigated.

Methods: A single intravenous dose of 2 μg/0.

Radioimmunotherapy Targeting B7-H3 glioma models enhanced antitumor efficacy by Reconstructing the tumor microenvironment.

Radionuclide drug conjugates (RDCs) with antibodies serve as a novel approach for the treatment of malignant tumors including glioblastoma. However, RDCs require optimal antibodies to work efficiently. Hu4G4, a novel B7-H3-targeting humanized monoclonal IgG1 antibody, is highly specific for the human B7-H3 protein (a marker of tumor cells, including glioblastoma cells).

Exploring the complex relationship between vitamin K, gut microbiota, and warfarin variability in cardiac surgery patients.

Background And Objectives: Due to the high individual variability of anticoagulant warfarin, this study aimed to investigate the effects of vitamin K concentration and gut microbiota on individual variability of warfarin in 246 cardiac surgery patients.

Methods: The pharmacokinetics and pharmacodynamics (PKPD) model predicted international normalized ratio (INR) and warfarin concentration. Serum and fecal samples were collected to detect warfarin and vitamin K [VK1 and menaquinone-4 (MK4)] concentrations and gut microbiota diversity, respectively.