Safety, pharmacokinetics, and food-effect of pivmecillinam after single- and multiple-dose in healthy Chinese subjects: a phase I study.

Urinary tract infection (UTI) is one of the most prevalent bacterial infectious diseases worldwide. However, the resistance of urinary pathogens to other UTI antibiotics such as trimethoprim and trimethoprim/sulphamethoxazole increased. Pivmecillinam is a prodrug of mecillinam, which is effective for the treatment of urinary tract infections.

LC-MS/MS methods to quantify HCP002 in human plasma and urine: applications in a pharmacokinetic study.

HCP002, a phosphate-modified derivative of voriconazole, can improve solubility without using the nephrotoxic solubilizer, sulfobutylether-β-cyclodextrin. To study pharmacokinetics in humans, LC-MS/MS methods to quantify HCP002 in human plasma and urine were developed and validated. After protein precipitation by acetonitrile containing voriconazole-d, HCP002 was separated on a ZORBAX SB-Aq column, and LCMS/MS analysis was performed in multi-response monitoring mode.

Development and validation of a hydrophilic interaction liquid chromatography-tandem mass spectrometry method for the quantification of regadenoson in human plasma and its pharmacokinetic application.

Regadenoson, the first selective adenosine A receptor agonist, is used to perform exercise stress test during radionuclide myocardial perfusion imaging. To detect the concentration of regadenoson in human plasma, a simple, fast, and sensitive tandem mass spectrometry method was established herein. Acetonitrile was used as a protein precipitation agent.

Simultaneous Determination of Voriconazole and Its Voriconazole N-Oxide Metabolite in Human Urine by Liquid Chromatography/Tandem Mass Spectrometry.

A convenient and sensitive liquid chromatography-tandem mass spectrometry method was established to simultaneously quantify voriconazole (VRZ) and its metabolite, voriconazole N-oxide (VNO), in human urine. Voriconazole-d3 and voriconazole-d3 N-oxide were used as isotopic internal standards. Samples were processed by protein precipitation and separated using a ZORBAX SB-Aq column (1.

Impact of CYP2C19 genotype on voriconazole exposure and effect of voriconazole on the activity of CYP3A in patients with haematological malignancies.

Voriconazole (VRC) is a first-line drug for the treatment of invasive fungal infections (IFIs) and an inhibitor of CYP3A activity. The aims of this study are to investigate the influence of related factors on the plasma concentration of voriconazole and the effect of voriconazole on the activity of CYP3A in patients with haematological malignancies.A total of 89 patients received an initial dose of 6 mg/kg followed by 4 mg/kg every 12 h were included in the study.

Pharmacogenetic and safety analysis of cinacalcet hydrochloride in healthy Chinese subjects.

Background: Our study aims to explore the effect of genetics on the pharmacodynamics (PD) and pharmacokinetics (PK) of cinacalcet in healthy Chinese subjects; to investigate the effect of dietary factors on cinacalcet, and to evaluate the safety of cinacalcet under fasting and non-fasting conditions using a bioequivalence trial.

Methods: We investigated the relationship of cinacalcet PK with single nucleotide polymorphisms (SNPs) of CYP3A4, CYP1A2 and CYP2D6, and of cinacalcet PD with SNPs of calcium-sensitive receptors (CASR) and vitamin D receptors (VDR) in 65 healthy Chinese subjects recruited to participate in this study. Our study was a phase I, open-label, randomized, two-period, two-sequence crossover, a single-center clinical study designed under both fasting and non-fasting conditions to investigate the effect of dietary factors on cinacalcet.

Tolerability, Safety, Pharmacokinetics and Drug Interaction of Cefotaxime Sodium-Tazobactam Sodium Injection (6:1) Following Single and Multiple Intravenous Doses in Chinese Healthy Subjects.

Purpose: To evaluate the tolerability, safety, pharmacokinetics and drug interaction of cefotaxime sodium-tazobactam sodium injection (6:1) in Chinese healthy subjects. The results of the safety and pharmacokinetic studies supported further clinical trials.

Method: A randomized, single-blind, ascending dose, placebo-controlled, single-center study was conducted.

Effects of ABCB1, UGT1A1, and UGT1A9 Genetic Polymorphisms on the Pharmacokinetics of Sitafloxacin Granules in Healthy Subjects.

Sitafloxacin, a new fluoroquinolone, has strong antibacterial activity. We evaluated the effects of sitafloxacin granules in single-dose and multidose cohorts and the effects of ABCB1, UGT1A1, and UGT1A9 genetic polymorphisms on the pharmacokinetics (PK) of sitafloxacin in healthy subjects. The single-dose study included 3 fasted cohorts receiving 50, 100, and 200 mg of sitafloxacin granules and 1 cohort receiving 50 mg of sitafloxacin granules with a high-fat meal.

mutation induced renal failure and polycystic kidney disease in a pair of childhood male twins in China.

Background: Oral-facial-digital syndrome type 1 (OFD1) is a rare ciliopathy mainly with an X-linked dominant pattern of inheritance, which is caused by mutations in the gene. The OFD1 protein is located within the centrosomes and basal bodies of the primary cilia. It is reported that approximately 15%-50% cases of OFD1 progress to end-stage renal disease (ESRD) following development of polycystic kidney diseases (PKD).

Effects of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of proton pump inhibitors.

Proton pump inhibitors (PPIs) are used widely for the treatment of acid-related disorders. Despite their excellent efficacy and tolerance, the pharmacodynamics and pharmacokinetics of PPIs are affected by each patient's CYP2C19 and gastric H,K-ATPase genotype. The aim of this review was to analyze the effect of genetic polymorphisms on the pharmacodynamic and pharmacokinetic properties of PPIs.

Perivascular adipose tissue dysfunction aggravates adventitial remodeling in obese mini pigs via NLRP3 inflammasome/IL-1 signaling pathway.

Perivascular adipose tissue (PVAT), a special type of adipose tissue, closely surrounds vascular adventitia and produces numerous bioactive substances to maintain vascular homeostasis. PVAT dysfunction has a crucial role in regulating vascular remodeling, but the exact mechanisms remain unclear. In this study, we investigated whether and how obesity-induced PVAT dysfunction affected adventitia remodeling in early vascular injury stages.

Impact of Gastric rs2733743 on the Intragastric pH-Values of Dexlansoprazole Injection in Chinese Subjects.

Not all patients with acid-related disorders receiving proton pump inhibitor (PP) treatment get adequate gastric pH control. The genetic variation of receptors, metabolic enzymes, and transporters are known to cause failures of therapies. We have conducted a study to evaluate the influence of gastric , and polymorphisms on the pharmacokinetic and pharmacodynamic profiles of dexlansoprazole injection in healthy Chinese subjects.

Astragaloside IV sensitizes non-small cell lung cancer cells to gefitinib potentially via regulation of SIRT6.

Astragaloside IV, the active component of Astragalus membranaceus, exhibits diverse biological roles including the anti-tumor activity. In this study, we evaluated the chemosensitive role of astragaloside IV in non-small cell lung cancer cells. Cell Counting Kit-8 analysis was performed to determine cell viability.

A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors.

Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H/K-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care.

Safety, tolerability, pharmacokinetics and pharmacodynamics of dexlansoprazole injection in healthy Chinese subjects.

Purpose: This study was conducted to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of dexlansoprazole injection in healthy subjects.

Methods: Dexlansoprazole (20-90 mg) or lansoprazole (30 mg) was administrated intravenously to healthy male and female volunteers. All the subjects were sampled for pharmacokinetic (PK) analysis and 64 of them were monitored for 24-h intragastric pH prior to and after administration in the pharmacodynamic (PD) study.