Exposure–Response Analysis of Osimertinib in EGFR Mutation Positive Non-Small Cell Lung Cancer Patients in a Real-Life Setting

Pharmaceutical Research - Osimertinib, an irreversible inhibitor of the epidermal growth factor receptor (EGFR) is an important drug in the treatment of EGFR-mutation positive non-small cell lung...     

Priming solutions for cardiopulmonary bypass: comparison of three colloids

The present study was designed to compare the differences in the clinical effects of three colloidal solutions, albumin, urea-linked gelatin, and succinyl-linked gelatin, when used as priming fluids for cardiopulmonary bypass (CPB) under alpha-stat conditions. A consecutive series of 105 patients scheduled for cardiac surgery were randomized into three identically managed groups, except for the CPB prime. Variables relating to acid-base status, oncotic activity, metabolism, coagulation, and postoperative evaluation were measured. Marked differences in acid-base status, colloid osmotic pressure, additional prime requirements, blood lactate, urine output, and the need for buffer solutions occurred among groups, with the succinyl-linked gelatin group having better results than the other groups. Changes in hemodynamics, oxygen consumption, and blood-glucose levels during CPB did not vary among groups. There were also no important intergroup differences in hematologic and clotting variables or postoperative parameters such as blood loss or use of blood products. Electrolyte changes were similar except for a significant increase in ionized calcium that occurred in the urea-linked gelatin group after bypass. The results indicate that succinyl-linked gelatin is an adequate and safe alternative to human albumin for use as a colloid during CPB under alpha-stat conditions.     

Real-time trace gas sensing of ethylene, propanal and acetaldehyde from human skin in vivo

Trace gases emitted by human skin in vivo are monitored non-invasively and in real time using laser-based photoacoustic detection and proton-transfer reaction mass spectrometry. A small quartz cuvette is placed on the skin to create a headspace from which a carrier gas transports the skin emissions to the detection systems. The transparency of quartz to ultraviolet radiation (UVR) allows investigation of UVR-related trace gas emissions. As a demonstration of this measurement system, the effect of supplemental intake of systemic antioxidants on UVR-induced lipid peroxidation is investigated. The production by the skin of three biomarkers of UVR-induced lipid peroxidation (ethylene, acetaldehyde and propanal) is monitored. Although no significant effect of antioxidant intake was observed, the method presented here is a novel and promising technique for investigation of human skin in vivo.     

Pharmacokinetics of ethylene in man by on-line laser photoacoustic detection

The pharmacokinetics of ethylene are determined using laser-based photoacoustic detection and a closed chamber setup. Concentration-time data are analyzed using a two-compartment and a physiologically based pharmacokinetic (PBPK) model. Endogenous production was 92 +/- 13 pmol/h/kg for the two-compartment model and 75 +/- 10 pmol/h/kg for the PBPK model. These values agree with previous work at our department but are significantly lower than published values based on gas chromatography. The blood:air partition coefficient in the PBPK model was determined by curve fitting, because simulations based on published values did not agree well with data. Curve fitting gave a value of 0.092 +/- 0.029. The real-time nature and high sensitivity of photoacoustic detection make it a useful addition to gas chromatography in closed chamber studies.