Therapeutic drug monitoring of posaconazole delayed-release tablets and injections in pediatric patients.

This study aimed to investigate the dose and trough concentration () of posaconazole delayed-release tablets and injections, and their correlation with efficacy and safety in pediatric patients. Patients younger than 18 years old received posaconazole delayed-release tablets or injections for prophylaxis or treatment of invasive fungal disease (IFD). Blood samples were collected to determine the plasma s, and dose regimen adjustments were made if necessary.

Cost-effectiveness analysis of dinutuximab β for the treatment of high-risk neuroblastoma in China.

Background: Dinutuximab β can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab β is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab β in children with high-risk NB is of high importance.

Simultaneous quantification and pharmacokinetics of vincristine and its major metabolite M1 in Chinese pediatric ALL patients by LC-MS/MS.

Vincristine (VCR) is a vital component in numerous treatment regimens for pediatric blood cancer. VCR-induced peripheral neuropathy (VIPN) represents a type of VCR toxicity influenced by multiple factors, including age, race, genetic traits, dosage, interactions, and administration regimen. However, the dose-response relationship of VIPN remains elusive.

Pharmacokinetics of Novel Furoxan/Coumarin Hybrids in Rats Using LC-MS/MS Method and Physiologically Based Pharmacokinetic Model.

Novel furoxan/coumarin hybrids were synthesized, and pharmacologic studies showed that the compounds displayed potent antiproliferation activities via downregulating both the phosphatidylinositide 3-kinase (PI3K) pathway and the mitogen-activated protein kinase (MAPK) pathway. To investigate the preclinical pharmacokinetic (PK) properties of three candidate compounds (CY-14S-4A83, CY-16S-4A43, and CY-16S-4A93), liquid chromatography, in tandem with the mass spectrometry LC-MS/MS method, was developed and validated for the simultaneous determination of these compounds. The absorption, distribution, metabolism, and excretion (ADME) properties were investigated in in vitro studies and in rats.

Application of Physiologically Based Pharmacokinetic Modeling in Preclinical Studies: A Feasible Strategy to Practice the Principles of 3Rs.

Pharmacokinetic characterization plays a vital role in drug discovery and development. Although involving numerous laboratory animals with error-prone, labor-intensive, and time-consuming procedures, pharmacokinetic profiling is still irreplaceable in preclinical studies. With physiologically based pharmacokinetic (PBPK) modeling, the profiles of drug absorption, distribution, metabolism, and excretion can be predicted.

A Novel Method for Predicting the Human Inherent Clearance and Its Application in the Study of the Pharmacokinetics and Drug-Drug Interaction between Azidothymidine and Fluconazole Mediated by UGT Enzyme.

In order to improve the benefit-risk ratio of pharmacokinetic (PK) research in the early development of new drugs, in silico and in vitro methods were constructed and improved. Models of intrinsic clearance rate (CL) were constructed based on the quantitative structure-activity relationship (QSAR) of 7882 collected compounds. Moreover, a novel in vitro metabolic method, the Bio-PK dynamic metabolic system, was constructed and combined with a physiology-based pharmacokinetic model (PBPK) model to predict the metabolism and the drug-drug interaction (DDI) of azidothymidine (AZT) and fluconazole (FCZ) mediated by the phase II metabolic enzyme UDP-glycosyltransferase (UGT) in humans.

Correlation of L-asp Activity, Anti-L-asp Antibody, Asn and Gln With Adverse Events Especially Anaphylaxis Risks in PEG-asp-Contained Regime Treated Pediatric ALL Patients.

Objective: This study aimed to investigate the correlation of L-asparaginase (L-asp) activity, anti-L-asp antibody, asparagine and glutamine levels with the risks of adverse events (AEs), especially anaphylaxis, in pediatric acute lymphoblastic leukemia (ALL) patients who underwent polyethylene glycol-conjugated L-asp (PEG-asp)-contained treatment.

Methods: Plasma samples were collected from 91 pediatric ALL patients who underwent PEG-asp-contained treatment on the 7th day after drug administration. Plasma L-asp activity, anti-L-asp antibody level, asparagine level and glutamine level were detected.

Neutrophil to lymphocyte rate and serum prealbumin maybe predictors for abnormal high blood pressure caused by adrenocorticotropic hormone therapy in children with epileptic spasms: two cases report.

Epileptic spasms are a catastrophic form of epilepsy. When epileptic spasms occur under 2-year-old, they may be also called "infantile spasms". Adrenocorticotropic hormone (ACTH) is recommended as first line intervention for the treatment of epileptic spasms without tuberous sclerosis complex.

Grape seed proanthocyanidin extract reverses multidrug resistance in HL-60/ADR cells via inhibition of the PI3K/Akt signaling pathway.

Background And Purpose: Multidrug resistance (MDR) is a great challenge and obstacle in cancer treatment. It is a common problem in the treatment of acute myeloid leukemia (AML). Whether grape seed proanthocyanidin extract (GSPE) could reverse MDR in patients with AML is still unknown.

Rs4846049 Polymorphism at the 3'-UTR of MTHFR Gene: Association with Susceptibility to Childhood Acute Lymphoblastic Leukemia.

Background: Accumulating evidence has suggested the polymorphisms of methylenetetrahydrofolate reductase (MTHFR) were associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). However, the known conclusions of currently known polymorphic loci (677 C > T and 1298 A > C) remain controversial. This study was to investigate new genetic biomarkers for ALL by analyzing the MTHFR polymorphisms at the 3'-untranslated region, which is a location bound by miRNAs.

[G protein-coupled receptor 17 is involved in CoCl-induced hypoxic injury in RGC-5 cells].

Objective: To investigate the effect of G protein-coupled receptor 17 (GPR17) on hypoxia injury in retinal ganglion cells .

Methods: CoCl (400 μmol/L) was used to induce hypoxic injury in RGC-5 cells. The expression of GPR17 and the effect of GPR17 ligands were investigated, and the role of GPR17 in hypoxia injury was further studied by transfection of RGC-5 cells with GPR17 small interfering RNA (siRNA).

Protocol for a systematic evaluation of pediatric pharmacy development and pediatric pharmacy experts' research area in China.

Background: The pediatric pharmacy research status of children's hospitals in China is still unknown. Our previous findings suggest the regional differences in academic level in tertiary (grade III level A) children's hospitals in China.

Methods: This systemic evaluation described in this protocol will be conducted to follow the Cochrane Handbook.

Probiotic Supplementation for Prevention of Atopic Dermatitis in Infants and Children: A Systematic Review and Meta-analysis.

Background: Probiotic supplementation in early life may be effective in preventing atopic dermatitis (AD); however, results regarding efficacy have been controversial.

Objective: The aim of our study was to investigate the effect of probiotic supplementation on the risk of AD.

Methods: We systematically searched PubMed, EBSCO, Embase and Web of Science databases up to 8 March 2018 for potentially relevant studies regarding probiotic supplementation and AD.

Warfarin and the Risk of Death, Stroke, and Major Bleeding in Patients With Atrial Fibrillation Receiving Hemodialysis: A Systematic Review and Meta-Analysis.

Up to date, the efficacy and safety of warfarin treatment in atrial fibrillation patients receiving hemodialysis remain controversial. So we performed this meta-analysis to try to offer recommendations regarding warfarin management in this population. We searched Pubmed, Embase, and Cochrane library and reviewed relevant reference lists from 1980 to March 2018.

αβ integrin inhibitors: a patent review.

The αβ integrin is heterodimeric cell surface receptors expressed on most leukocytes. Mucosal addressing cell adhesion molecule 1(MAdCAM-1) is an exclusive ligand for αβ integrin. Areas covered: This article will highlight the progress that has been made in the discovery and development of αβ integrin inhibitors, and their use in the treatment of inflammatory bowel diseases, multiple sclerosis, asthma, hepatic disorders, human immunodeficiency virus, allergic conjunctivitis and type 1 diabetes.

Clinical adverse effects of sodium-glucose cotransporter 2 inhibitors: Protocol for a systematic review and meta-analysis.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral antidiabetic drugs, which mainly increase urinary glucose excretion through reducing renal glucose reabsorption. There is still a concern about the overall safety profile of SGLT2 inhibitors. In this systematic review and meta-analysis, we will assess the clinical adverse effects of SGLT2 inhibitors in type 2 diabetes mellitus.

Clinical adverse effects of natalizumab: Protocol for a meta-analysis of randomized double-blind placebo-controlled clinical trails.

Background: Natalizumab (NAT), a humanized monoclonal antibody, which binds in both α4β1 integrins and α4β7 integrins, is approved for the treatment of multiple sclerosis (MS) and Crohn's disease (CD). An uncommon but serious adverse event from NAT treatment is known as progressive multifocal leukoencephalopathy (PML). However, clinical comprehensive safety evidence of NAT is limited.

A Review on Clinical Pharmacokinetics, Pharmacodynamics, and Pharmacogenomics of Natalizumab: A Humanized Anti-α4 Integrin Monoclonal Antibody.

Background: Natalizumab (NAT), a humanized monoclonal antibody, binding in both α4β1 and α4β7 integrins, is approved for the treatment of Multiple Sclerosis (MS) and Crohn's Disease (CD). This review highlights the detailed Pharmacokinetics (PK) and Pharmacodynamics (PD) information of NAT, with the Pharmacogenomics (PG) properties of NAT.

Methods: We undertake a systemic English-language search of Medline, EMBASE, Cochrane Library electronic databases to identify all potential studies with PK, PD or PG properties of NAT (up to October 2017).

Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population.

Background: The aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL).

Methods: A case-control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

The pharmacokinetic profiles of dexamethasone and methylprednisolone concentration in perilymph and plasma following systemic and local administration.

Conclusion: Both methylprednisolone (MTH) and dexamethasone (DEX) could successfully and effectively penetrate the round window membrane (RWM) into perilymph. RWM topical application and otocyst infusion with MTH and DEX result in high perilymph drug concentrations and low plasma levels. An intratympanic administration schedule for DEX or MTH could be carried out twice daily.