High-fidelity single logical qubit encoding scheme assisted by single-sided quantum dot-cavity systems.

We present an encoding scheme of a single logical qubit with single-sided quantum dot (QD)-cavity systems, which is immune to the collective decoherence. By adjusting the Purcell factor to satisfy the balanced reflection condition, the detrimental effects of unbalanced reflection between the coupled and uncoupled QD-cavity systems can be effectively suppressed. Furthermore, the fidelity of each step can be increased to unity regardless of the strong coupling regime and the weak coupling regime of cavity quantum electrodynamics (QED) with the assistance of waveform correctors. The scheme requires QD-cavity systems and simple linear optical elements, which can be implemented with the currently experimental techniques.

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. Plasma cinacalcet concentrations were analyzed using a validated HPLC-MS/MS assay. Clinical laboratory tests evaluated safety. Thirteen SNPs of CASR, VDR, and CYP genes were selected for pharmacogenetic analysis. RESULTS: CYP3A4 rs4646437 was found to be associated with the PK of cinacalcet under fasting conditions (P<0.01). Subjects carrying T alleles of rs4646437 appeared to metabolize cinacalcet poorly. The Cmax and AUC of subjects in the non-fasting group were significantly higher (P<0.0001) than those in the fasting group. The Tmax, CL/F, and Vd/F in the fasting group were significantly higher (P<0.0001) than those in the non-fasting group. In the fasting group, the geometric least square mean ratios (T/R) of the Cmax and AUC0-t were 109.89% and 105.33%, and the corresponding 90% CIs were 98.36-122.79% and 98.04-113.15%, respectively. In the non-fasting group, the T/R of the Cmax and AUC0-t were 100.74% and 99.09%, and the corresponding 90% CIs were 92.65-109.54% and 94.79-103.58%, respectively. All adverse events (AEs) were mild, and no serious adverse events (SAEs) occurred during the bioequivalence trial. CONCLUSIONS: Following our investigation, we reached the following conclusions: CYP3A4 rs4646437 may affect cinacalcet PK; the reference and test preparations of cinacalcet were bioequivalent under fasting and non-fasting conditions and were safe to use; and dietary factors had a significant effect on the PK of cinacalcet, in that exposure to the drug increased when cinacalcet was taken after eating.

The Impact of Plasma Protein Binding Characteristics and Unbound Concentration of Voriconazole on Its Adverse Drug Reactions.

This study investigated voriconazole (VRC) unbound plasma concentration and its relationship with adverse drug reactions (ADRs) in patients with malignant hematologic disease. Plasma samples were collected from patients or spiked in vitro. A time-saving rapid equilibrium dialysis assay was used for the separation of unbound and bound VRC, following a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis method for drug concentration detection. Liver function and treatment details were collected from the electronic medical records of patients. Protein concentration was determined according to instructions. VRC plasma protein binding rate (PPB) in patient is significantly higher [69.5 ± 6.2%] than that in in-vitro samples, influenced by total drug concentration (Ct), plasma protein concentration, and protein type. The α1-acid glycogen (AAG) has the highest affinity with VRC. Relationship between total PPB of VRC with PPB of individual protein is not a simple addition, but a compressive combination. Unbound drug concentration (Cu) of VRC shows significant relationships with Ct, protein concentration, AST level, metabolism type of CYP2C19 and co-administration of high PPB medicines. Unbound plasma concentration of VRC shows a more sensitive relationship with ADRs than Ct.

Impact of 14 types of genetic polymorphisms on antihypertensive efficacy of felodipine in healthy Chinese subjects
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OBJECTIVE: This study evaluated different influences of 14 single nucleotide polymorphisms (SNPs) and demographic factors leading to individual differences in the antihypertensive efficacy of felodipine in healthy Chinese subjects. MATERIALS AND METHODS: 24 subjects were sequenced for candidate SNPs. Plasma samples were obtained as clinical trial protocol, and were determined by a HPLC-MS/MS method. Pharmacokinetic parameters were calculated by WinNonlin 6.0. Statistical analysis was mainly performed by SPSS 22.0. A multiple linear regression model provided different weight coefficients of different demographic and genetic factors. RESULTS: The trend of Cmax is almost consistent with AUCss increase, but tmax of individuals is different; the antihypertensive effect of felodipine is individually different. A significant association was observed between systolic blood pressure decrease (ΔSBP) and SNPs of CACNA1C, CACNA1D, GNB3 respectively, while CACNA1C and CACNA1 were associated with diastolic blood pressure decrease (ΔDBP). CYP3A5 rs766746 and CYP3A4 rs2242480 were linked with Cmax and AUCss, and ABCB1 rs1045642 was associated with T1/2. Significant relationships were shown between AUCss and ΔSBP (p = 0.022) as well as Cmax and ΔSBP (p = 0.015). CONCLUSION: The efficacy of felodipine is individually different, influenced especially by CACNA1C rs1051375 and ABCB1 rs1045642. ΔDBP is associated with ΔSBP in multiple-dosing of felodipine in healthy Chinese subjects.

Genetic Polymorphism on the Pharmacokinetics and Pharmacodynamics of Platelet-derived Growth Factor Receptor (PDGFR) Kinase Inhibitors.

BACKGROUND: Platelet-derived Growth Factor Receptor (PDGFR) is a kind of Receptor Tyrosine Kinases (RTKs). PDGFR Tyrosine Kinase Inhibitors (TKIs) which are small molecule inhibitors targeting PDGFR prevent and block cell proliferation signal transduction pathways. Recently, there have been 11 TKIs (including imatinib, sunitinib, regorafenib, sorafenib, pazopanib, axitinib, dasatinib, nilotinib, lenvatinib, cabozantinib and ponatinib) targeting PDGFR approved by FDA for the treatment of chronic myelogenous leukemia, gastrointestinal stromal tumors, renal cell carcinoma et al. Pharmacokinetics (PK) reflects the processes of drugs in body, while pharmacodynamics (PD) reflects the efficacy. Genetic polymorphisms of metabolizers and transporters contribute to highly inter-individual variability in PK and PD. This review aims to introduce the clinical applications, instruction and usage, PK, PD and pharmacogenetics of these PDGFR TKIs. METHODS: In vivo and in vitro studies about PDGFR TKIs were searched from PubMed. Data and information were analyzed and summarized. RESULTS: The overview of (1) general information on PDGFR kinase inhibitors; (2) PK parameters of PDGFR kinase inhibitors; (3) metabolic enzymes and transporters of PDGFR kinase inhibitors; (4) main drug interactions of PDGFR kinase inhibitors; (5) adverse events of PDGFR kinase inhibitors; and (6) genetic polymorphism on PK and PD of PDGFR kinase inhibitors, was exhibited and discussed in this review. CONCLUSION: This review summarized the general information, PK, metabolic enzymes and transporters, main drug interactions, adverse events and pharmacogenetics of FDA approved PDGFR TKIs. Studies showed that Single nucleotide polymorphisms of metabolic enzymes and transporters had influence on the PK and PD of PDGFR TKIs.

Safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole sodium injections after single and multiple intravenous doses in healthy Chinese subjects.

PURPOSE: The objective of this study was to evaluate the safety, pharmacokinetics, and pharmacodynamics of S-(-)-pantoprazole (PPZ) sodium injections following single and multiple intravenous doses in healthy Chinese subjects. METHODS: The dosage groups were set as followed: 20 mg of single and multiple intravenous administration of S-(-)-PPZ, 40 mg of single and multiple intravenous administration of S-(-)-PPZ or pantoprazole, and 80 mg of single dosage group of S-(-)-PPZ. Subjects were sampled for pharmacokinetic analysis and were monitored for 24-h intragastric pH prior to and 48-h intragastric pH after administration for the pharmacodynamic study. The pharmacokinetic and pharmacodynamic parameters were compared between S-(-)-PPZ and PPZ. Safety was evaluated on the basis of adverse events, vital signs, laboratory tests, and physical examination. RESULTS: All adverse events were mild and of limited duration. Maximum plasma concentration and area under the concentration-time curve for S-(-)-PPZ were dose proportional over the range of 20-80 mg following a single intravenous administration. Elimination rate constant and half-life observed statistical difference from a single dose to multiple doses in 40 mg of S-(-)-PPZ groups. After administration of a single dose, the mean 24-h intragastric pH value was observed higher in 80-mg group than in 40- and 20-mg groups. Slightly increase of intragastric pH was found after a single dose of 40 mg S-(-)-PPZ than 40 mg PPZ; however, the differences were not statistically significant. CONCLUSIONS: Twice daily of 40 mg S-(-)-PPZ sodium injections is effective in achieving satisfying acid inhibition. Compared with plasma R-(+)-PPZ levels, most subjects presented more potent and prolonged suppression of gastric acid of S-(-)-PPZ, while a few subjects showed faster metabolic rate of S-(-)-PPZ in vivo.

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. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.

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. RESULTS: Maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC0-τ) for dexlansoprazole injection was dose-proportional over the range of 20-90 mg following a single intravenous administration. Total clearance and half-life (t1/2) was independent of dose, and ranged from 4.69 L/h to 5.85 L/h and from 1.24 h to 2.17 h, respectively. A single dose of dexlansoprazole (30 mg) resulted in higher gastric pH compared to that of lansoprazole, evidenced by a mean 24-h gastric pH of 6.1 ± 1.2 (lansoprazole: 5.4 ± 1.1) and 24-h gastric pH > 6 post drug dose holding time of 64.2 ± 21.0% (lansoprazole: 49.5 ± 21.5%). CONCLUSION: Dexlansoprazole injection was safe and well tolerated for up to 5-day repeated intravenous administration dose of 30 mg. The recommended dosage for dexlansoprazole injection is 30 mg for an adequate gastric acid control.

Stable and extreme resistance to common scab of potato obtained through somatic cell selection.

Somatic cell selection with thaxtomin A as a positive selection agent was used to isolate variants of potato cv. Russet Burbank with strong to extreme resistance to common scab. Glasshouse and field trials identified 51 variants with significantly reduced disease incidence (frequency of infected tubers) and severity (tuber lesion coverage) compared with the parent cultivar. The most promising variants exhibited extreme disease resistance, rarely showing lesions, which were invariably superficial and shallower than those on the parent. Resistance traits were consistently expressed both in 10 glasshouse and two field trials at different locations, with varied inoculum and disease pressure. Disease-resistant variants differed in their response to thaxtomin A in tuber slice bioassays. Of 23 variants tested, 10 showed reduced thaxtomin A susceptibility, with the remaining 13 responding similar to that of the parent. Thus, toxin tolerance was not the only factor responsible for observed disease resistance; however, four of the five most disease-resistant variants had enhanced thaxtomin A tolerance, suggesting that this factor is important in the expression of strong disease resistance. Pathogenicity and toxin tolerance remained stable over a 6-year period, demonstrating that selected phenotypes were robust and genetic changes stable. The majority of disease-resistant variants had tuber yields equivalent to the parent cultivar in glasshouse trials. This suggests that selection for disease resistance was not associated with negative tuber attributes and that certain variants may have commercial merit, worthy of further agronomic testing.