Search

Objective: Pyrotinb has been approved for the treatment of HER2-positive advanced or metastatic breast cancer in China. However, the plasma concentration of pyrotinb in different patients varies greatly, and in the course of treatment, if patients have intolerable adverse reactions, the drug dosage will be reduced or even stopped. This study set out to establish an ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the determination of pyrotinb in human plasma, analyze the population pharmacokinetics (PPK) of pyrotinib and assess the influence of patient variables on PK of pyrotinib in patients with HER2 positive breast cancer. Method: An UPLC-MS/MS method was developed to measure pyrotinib in human plasma. Utilizing a gradient elution procedure and a Kinetex C18 column (2.1 mm × 100 mm, 1.7 μm), sample separation was accomplished in 5.5 min. Pyrotinb extraction via protein precipitation was used as a sample pre-treatment technique. In total, 50 patients provided 158 plasma samples, which were identified and used in the PPK investigation. The non-linear mixed-effects modeling (NONMEM) approach was used to assess the plasma concentrations and covariates information. For the final PPK model evaluation, external evaluation, non-parametric bootstrap, visual predictive check (VPC), and goodness-of-fit (GOF) were used. Results: The UPLC-MS/MS method for determining plasma concentration of pyrotinib in patients had good selectivity and linearity in the range of 1–1,000 ng/mL. Pyrotinib concentration profile in HER2-positive breast cancer patients was well described by a single-compartment PPK model with first-order absorption and elimination. The formulas for the final estimated values of overall parameters of CL/F and Vd/F and Ka are respectively: C L / F L / h = 88.8 × e TP / 67.2 × 0.376 , V / F L = 3940 , K A h − 1 = 0.357 F I X E D. No dosage adjustment was advised, despite the possibility that the total protein levels could have a substantial impact on the apparent distribution volume of pyrotinib with limited magnitude. Conclusion: In this study, an UPLC-MS/MS method was established to determine the concentration of pyrotinib in human plasma. A population pharmacokinetic model of pyrotinib in HER2 positive breast cancer patients suggested that low serum total protein reduced the clearance rate of pyrotinib in patients. Clinical medical staff should pay attention to the liver function of patients with abnormal serum total protein and be alert to the occurrence of adverse drug reactions. [ABSTRACT FROM AUTHOR]

The inner roller exerts a supportive and thinning effect on the inner side of the tube during counter-roller spinning. In this paper, the Finite Element Analysis (FEA) model of counter-roller spinning for a 6061 aluminum alloy tube was established based on the ABAQUS/Explicit module. The deformation characteristics and the influence of inner roller geometrical parameters on the tube spinning were analyzed. The results showed that the stress–strain on the outer of the tube was greater than that of the inner, and flaring was more prone to occur in the initial stage of counter-roller spinning compared to traditional mandrel spinning. The order of the effects of geometrical parameters of the inner roller on the roundness error and wall thickness deviation was as follows: nose radius > diameter > front angle. The order of factors influencing the inner and outer spinning force was as follows: diameter > nose radius > front angle. Increasing the diameter of the inner roller can improve the spinning stability and forming accuracy of counter-roller spinning. It was beneficial to improve the forming accuracy when the nose radius of the inner roller was slightly larger than that of the outer roller. The front angle of the inner roller has little influence on the spinning forming accuracy. [ABSTRACT FROM AUTHOR]

Multistage fracturing in horizontal well has become one of the important techniques for the efficient development of low-permeability sandstone reservoirs. In multistage hydraulic fractured horizontal wells (MHFHWs), the depth of fracturing fluid invasion into the formation is a key parameter evaluating the imbibition enhancement after fracturing. However, few studies have been conducted on the invasion depth of fracturing fluids combining experiments and mathematical models under high-pressure differences in MHFHWs. Therefore, in this work, a mathematical model with experimental validation is proposed for evaluating the fracturing fluids invasion under high pressure. We first conducted a series of displacement experiments under different pressure differences to obtain the breakthrough time and invasion velocity. All core samples are taken from the block X of Xinjiang oilfield. A mathematical model of fracturing fluid injection was then established, considering the two-dimensional filtration of fracturing fluid. Then, the calculated invasion velocity was validated against the experimental data. Afterward, the invasion depth and invasion volume were determined for this typical horizontal well. Results show that at the end of 72 min, the invasion depth reaches 1.516 m when measured by core experiments and 1.434 m when calculated by the proposed model. The total invasion volume of all fracturing stages is estimated as 21,560.05 m3 and the actual total fluid volume injected is 24,019.6 m3. The paper formed a scientific and reasonable evaluation method of fracturing fluid invasion depth during the fracturing of horizontal wells, which provides solid theoretical support for the effective evaluation of fracturing to improve oil recovery. [ABSTRACT FROM AUTHOR]