Stagecantu1070

l purpose as both a drug delivery carrier and a pulmonary surfactant in treating pulmonary metastasis.We previously described the development of potent μ-opioid receptor (MOR)-agonist/δ-opioid receptor (DOR)-antagonist peptidomimetic ligands as an approach toward effective analgesics with reduced side effects. In this series, a tetrahydroquinoline (THQ) or substituted phenyl is employed to link two key pharmacophore elements, a dimethyltyrosine amino acid and typically an aromatic pendant. Using new and previously reported analogues, we constructed a structure-activity relationship (SAR) matrix that probes the utility of previously reported amine pendants. This matrix reveals that the MOR-agonist/DOR-antagonist properties of these ligands do not change when a tetrahydroisoquinoline (THIQ) pendant is used, despite removal of substituents on the core phenyl ring. Based on this observation, we retained the THIQ pendant and replaced the phenyl core with simpler aliphatic chain structures. These simpler analogues proved to be potent MOR-agonists with high variability in their effects at the DOR and the κ-opioid receptor (KOR). These data show that the amine of the THIQ pendant may be a novel pharmacophore element that favors high MOR-efficacy, whereas the aromatic ring of the THIQ pendant may produce high MOR-potency. Combined, the two pharmacophores within the THIQ pendant may be a structurally efficient means of converting opioid peptides and peptidomimetics into potent and efficacious MOR-agonists.

In children with cystic fibrosis (CF), the currently recommended amikacin dose ranges between 30-35 mg/kg/day; however, data supporting this dosing efficacy is lacking. Herein, the objectives were to develop a non-parametric pharmacokinetic population model (POPPK) for amikacin in children with CF and investigate the efficacy and toxicity at different dose rates for distinct minimum inhibitory concentration (MIC) clinical breakpoints using Monte Carlo simulations.

Data from 94 children with CF (613 serum concentrations) from the Bordeaux University Hospital's CF-centre (CRCM) were analyzed. After determination of POPPK parameters and associated influent covariates in Pmetrics, 1000 Monte Carlo simulations were performed for 7 different dose rates between 30 and 60 mg/kg/day, to predict the probability of obtaining peak serum amikacin ≥10 × MIC and trough level ≤ 2.5 mg/L, for MIC values between 1 and 16 mg/L.

The median[min-max] age and weight were 10[0.3-17] years and 29[6-71] kg, respectively, with onwith an acceptable calculated residual trough level in cases of normal or hyperfiltration. As amikacin undergoes renal clearance, which is immature until one year of age, dosing recommendations for this age group may be markedly high, warranting cautious interpretation.

Cannabidiol (CBD) is a non-psychoactive natural product that has been used increasingly as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children.

To develop and validate an ultra-fast ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients.

Eight-point CBD calibration curves were prepared using 60 µL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70% to 90% gradient of ACN in 2 min. Multiple reaction monitoring transitions of major CBD and THC metabolsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.

and study The utility of measuring thiopurine metabolites (TM) to individualize therapy in autoimmune hepatitis (AIH) has not been defined, and the evidence regarding its use in clinical practice is heterogeneous. This systematic review and meta-analysis aimed to compare the mean concentration of TM between patients in biochemical remission and those not in remission.

A systematic literature search was conducted using PubMed, Scopus, the Cochrane Library, and Google Scholar for keywords related to TM and AIH. Selleck Isuzinaxib Two reviewers independently searched and selected studies comparing the levels of 6-methyl mercaptopurine (6-MMP) and 6-thioguanine nucleotide (6-TGN) and their ratio in cases of AIH in remission and otherwise. Meta-analysis was performed by calculating the weighted mean difference using the inverse variance heterogeneity model.

A total of 1066 records were identified through systematic search, of which 7 (n = 3 pediatric, n = 4 adults) were considered for inclusion and 442 TM measurements (n = 128t-off of 6-TGN.

Dose escalation of adalimumab (ADA) for loss or response in inflammatory bowel disease (IBD) is a common practice. Recent data suggest improved outcomes with an ADA concentration of 12 μg/mL, but limited data are available on the ability to achieve a target concentration. The aim of this study was to determine the expected change in serum ADA concentration following a dose escalation performed every seven days in patients with IBD.

A retrospective cohort of patients with IBD receiving ADA was divided into every fourteen-day dosing, every seven-day dosing, and dose escalation (i.e., q14 to q7 day dosing). The primary outcome was the change in ADA concentration. Multiple logistic regression was performed to identify predictors of achieving a target ADA concentration of ≥ 12 μg/mL.

Overall, 380 patients were identified, of whom 200 underwent dose escalation, 100 remained on q14 day dosing, and 80 were maintained on q7 day dosing. After dose escalation, the mean ADA concentration increased by 5.5 μg/mL (P &lation.

This article aims to review current evidence on the development, diagnosis, and management of retinal pigment epithelium (RPE) tear during anti-vascular endothelial growth factor (VEGF) therapy.

Literature searches were performed using MEDLINE/PubMed databases (cut-off date August 2019).

Three key recommendations were made based on existing literature and clinical experience 1) Multimodal imaging with color fundus photography, optical coherence tomography, near-infrared reflectance imaging, fundus autofluorescence imaging, optical coherence tomography-angiography, and/or fluorescein angiography are recommended to diagnose RPE tear and assess risk factors. Retinal pigment epithelium tears can be graded by size and foveal involvement. 2) Patients at high risk of developing RPE tear should be monitored after each anti-VEGF injection. If risk factors worsen, it is not yet definitively known whether anti-VEGF administration should be more frequent, or alternatively stopped in such patients. Prospective research into high-risk characteristics is needed.