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.

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.

Mass balance study of [C]SHR0302, a selective and potent JAK1 inhibitor in humans.

SHR0302, a selective JAK1 inhibitor developed by Jiangsu Hengrui Pharmaceutical Co., was intended for the treatment of rheumatoid arthritis. In this study, we evaluated the pharmacokinetics, mass balance, and metabolism of SHR0302 in six healthy Chinese male subjects after a single 8 mg (80 µCi) oral dose of [C]SHR0302.

A model based on machine learning for the prediction of cyclosporin A trough concentration in Chinese allo-HSCT patients.

Background: Cyclosporin A is a calcineurin inhibitor which has a narrow therapeutic window and high interindividual variability. Various population pharmacokinetic models have been reported; however, professional software and technical personnel were needed and the variables of the models were limited. Therefore, the aim of this study was to establish a model based on machine learning to predict CsA trough concentrations in Chinese allo-HSCT patients.

Development of Physiology Based Pharmacokinetic Model to Predict the Drug Interactions of Voriconazole and Venetoclax.

Purpose: Venetoclax (VEN), an anti-tumor drug that is a substrate of cytochrome P450 3A enzyme (CYP3A4), is used to treat leukemia. Voriconazole (VCZ) is an antifungal medication that inhibits CYP3A4. The goal of this study is to predict the effect of VCZ on VEN exposure.

Metabolic disposition of the EGFR covalent inhibitor furmonertinib in humans.

Furmonertinib was designed for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR T790M mutation. In this study, we investigated the metabolic disposition and mass balance in humans and tissue distribution in rats. After a single oral administration of 97.

Pharmacokinetics, mass balance, and metabolism of [C]vicagrel, a novel irreversible P2Y inhibitor in humans.

Vicagrel, a novel irreversible P2Y receptor inhibitor, is undergoing phase III trials for the treatment of acute coronary syndromes in China. In this study, we evaluated the pharmacokinetics, mass balance, and metabolism of vicagrel in six healthy male Chinese subjects after a single oral dose of 20 mg [C]vicagrel (120 µCi). Vicagrel absorption was fast (T = 0.

Feasibility study of Ga-labeled CAR T cells for in vivo tracking using micro-positron emission tomography imaging.

Clinical tracking of chimeric antigen receptor (CAR) T cells in vivo by positron emission tomography (PET) imaging is an area of intense interest. But the long-lived positron emitter-labeled CAR T cells stay in the liver and spleen for days or even weeks. Thus, the excessive absorbed effective dose becomes a major biosafety issue leading it difficult for clinical translation.

Multicenter-Based Population Pharmacokinetic Analysis of Ciclosporin in Hematopoietic Stem Cell Transplantation Patients.

Purpose: To explore the contribution of physiological characteristics to variability in ciclosporin pharmacokinetics in hematopoietic stem cell transplantation patients.

Methods: Clinical data from 563 patients were collected from centers in three regions. Ciclosporin concentrations were measured using immunoassays.

Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein.

Pyrotinib is a novel irreversible EGFR/HER2 dual tyrosine kinase inhibitor that is used to treat HER2-positive breast cancer. In this study we investigated the metabolism and disposition of pyrotinib in six healthy Chinese men after a single oral dose of 402 mg of [C]pyrotinib. At 240 h postdose, the mean cumulative excretion of the dose radioactivity was 92.

Theory-based pharmacokinetics and pharmacodynamics of S- and R-warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients.

Aims: The aims of this study are to apply a theory-based mechanistic model to describe the pharmacokinetics (PK) and pharmacodynamics (PD) of S- and R-warfarin.

Methods: Clinical data were obtained from 264 patients. Total concentrations for S- and R-warfarin were measured by ultra-high performance liquid tandem mass spectrometry.

Therapeutic Effect of Chenodeoxycholic Acid in an Experimental Rabbit Model of Osteoarthritis.

Osteoarthritis (OA) is a slowly progressive joint disease typically seen in middle-age to elderly people. At present, there is no ideal agent to treat OA. Chenodeoxycholic acid (CDCA) was a principal active constituent from animal bile.

Warfarin dosage adjustment strategy in Chinese population.

Background: Blood anticoagulation after heart valve replacement is a recognized difficulty all over the world. In this study, we identified the effect of amiodarone on the function of warfarin and confirmed the countermeasure by concluding the genotype distribution of vitamin K epoxide reductase complex 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) of the patient to predict the security dose of warfarin.

Methods: Studying on the VKORC1 (-1639G>A) and CYP2C9 genotype of 271 cases on heart valve replacement in the First Affiliated Hospital of Soochow University from Jan.

The genetic polymorphisms of POR*28 and CYP3A5*3 significantly influence the pharmacokinetics of tacrolimus in Chinese renal transplant recipients.

Purposes: The aims of this study were to assess the influence of the polymorphism of cytochrome P450 oxidoreductase (POR) as well as other relevant genes (CYP3A4, CYP3A5, ABCB1) on individual variability of tacrolimus pharmacokinetics and perform population pharmacokinetic analysis of tacrolimus in Chinese renal transplant recipients.

Methods: Tacrolimus trough whole blood concentrations and clinical details were retrospectively collected from 83 renal recipients. CYP3A4*1G, CYP3A5*3, and ABCB1 C3435T were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), POR*28 and CYP3A4*22 were genotyped by sequencing method.

Ginkgo biloba extracts attenuate lipopolysaccharide-induced inflammatory responses in acute lung injury by inhibiting the COX-2 and NF-κB pathways.

In the present study, we analyzed the role of Ginkgo biloba extract in lipopolysaccharide(LPS)-induced acute lung injury (ALI). ALI was induced in mice by intratracheal instillation of LPS. G.

A rapid and underivatized method for the determination of glutamine in human serum with ultra performance liquid chromatography-tandem mass spectrometry and its application.

A rapid and underivatized method for the determination of glutamine (Gln) in human serum was developed using ultra performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS). Gln was eluted in an Acquity UPLC BEH Amid column. The chromatographic separation was performed with an isocratic mobile phase consisting of acetonitrile and ammonium formate.

[Population pharmacokinetics and pharmacodynamics of clopidogrel in patients with acute coronary syndrome].

This study established a population pharmacokinetics-pharmacodynamics model of clopidogrel in patients with acute coronary syndrome. Fifty-nine patients were enrolled. The plasma concentration of clopidogrel active metabolite and vasodilator stimulated phosphoprotein platelet reactivity index (VASP-PRI) were selected as the pharmacokinetics index and the pharmacodynamics index, respectively.

Population pharmacokinetics and individualized dosage prediction of cyclosporine in allogeneic hematopoietic stem cell transplant patients.

Background: Cyclosporine (CsA), a potent immunosuppressive agent used to prevent rejection, is characterized by large individual variability. The purpose of this study was to explore the pharmacokinetic characteristics of CsA and establish a CsA population pharmacokinetic model that could be used for personalized therapy in allogeneic hematopoietic stem cell transplant (allo-HSCT) patients.

Methods: Clinical data were obtained from 117 allo-HSCT patients.

Association between the HLA-B*15:02 allele and carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Han individuals of northeastern China.

Background: This study examined the significant association between carbamazepine (CBZ)-induced Stevens-Johnson Syndrome (SJS)/toxic epidermal necrolysis (TEN) and HLA-B*15:02 in epilepsy patients of Han ethnicity living in northeastern China.

Methods: CBZ-SJS/TEN patients and CBZ-tolerant control patients were genotyped for HLA-B*15:02 by PCR amplification using sequence-specific primers. Patients then were evaluated for HLA genotypes using PCR with sequence-based typing.

Circadian variability of pharmacokinetics of cisplatin in patients with non-small-cell lung carcinoma: analysis with the NONMEM program.

Purpose: The aim of this study was to describe the nonlinear pharmacokinetics of total and unbound plasma cisplatin under different administered time in patients with non-small-cell lung carcinoma.

Methods: Patients receiving chemotherapy with cisplatin were included in this analysis. Patients were divided into two groups depending on the administrated time of cisplatin: 6:00 (Group A) and 18:00 (Group B).

Effects of enalapril on the expression of cardiac angiotensin-converting enzyme and angiotensin-converting enzyme 2 in spontaneously hypertensive rats.

Background: The discovery of angiotensin-converting enzyme 2 (ACE2) has greatly modified understanding of the renin-angiotensin system (RAS).

Aims: To investigate the cardiac expression of ACE2 and ACE in spontaneously hypertensive rats (SHRs) and the effects of enalapril on them.

Methods: Fifteen SHRs were randomly assigned to two groups: an SHR control group (n=7), treated with vehicle; and an enalapril group (n=8), treated with enalapril (15 mg/kg/day).