Frequency and Nature of Drug-Drug Interactions in the Intensive Care Unit.

Frequency and nature of drug-drug interactions in the intensive care unit.

Filed under: Drug and Alcohol Rehabilitation

Pharmacoepidemiol Drug Saf. 2013 Feb 18;
Askari M, Eslami S, Louws M, Wierenga PC, Dongelmans DA, Kuiper RA, Abu-Hanna A

PURPOSE: Drug-drug interactions (DDIs) may compromise patient safety. However, there are no good estimates of their frequency or understanding of their nature in the intensive care unit (ICU). The objective of this study was to determine the frequency and nature of potential DDIs (pDDIs) in the ICU when assessed in light of documented and perceived clinical relevance. METHODS: We developed a computerized algorithm to identify pDDI occurrence in ICU admissions with medication administration, on the basis of the Dutch national drug database. A panel of nine local pharmacists and intensivists completed questionnaires to classify the perceived relevance of the identified pDDI types for the ICU. A focus group discussed the conflicting classifications of relevance to reach consensus. For the pDDI types classified as relevant, we calculated their number and frequency per admission days. RESULTS: Out of 9644 admissions, 3892 had at least one pDDI. The pDDIs corresponded to 85 types, 36 of which were deemed relevant on the basis of the survey and focus group. These 36 types corresponded to 16?122 pDDIs (rate: 33.6 per 100 admission days) and 1084 unique admissions. PDDIs occurred in 11% of admissions to the general ICU, after limiting analysis to severe and relevant DDI types. The most frequently encountered drug classes were antithrombotic agents and antibacterials for systemic use. CONCLUSIONS: There are many potential DDIs with high perceived relevance in the ICU that appear to require attention and follow-up. Computerized decision support may help reduce the number of pDDIs but needs to be tailored to the environment in which it operates. Copyright © 2013 John Wiley & Sons, Ltd.
HubMed – drug

Bioinspired Patterning with Extreme Wettability Contrast on TiO(2) Nanotube Array Surface: A Versatile Platform for Biomedical Applications.

Filed under: Drug and Alcohol Rehabilitation

Small. 2013 Feb 18;
Lai Y, Lin L, Pan F, Huang J, Song R, Huang Y, Lin C, Fuchs H, Chi L

Binary wettability patterned surfaces with extremely high wetting contrasts can be found in nature on living creatures. They offer a versatile platform for microfluidic management. In this work, a facile approach to fabricating erasable and rewritable surface patterns with extreme wettability contrasts (superhydrophilic/superhydrophobic) on a TiO(2) nanotube array (TNA) surface through self-assembly and photocatalytic lithography is reported. The multifunctional micropatterned superhydrophobic TNA surface can act as a 2D scaffold for site-selective cell immobilization and reversible protein absorption. Most importantly, such a high-contrast wettability template can be used to construct various well-defined 3D functional patterns, such as calcium phosphate, silver nanoparticles, drugs, and biomolecules in a highly selective manner. The 3D functional patterns would be a versatile platform in a wide range of applications, especial for biomedical devices (e.g., high-throughput molecular sensing, targeted antibacterials, and drug delivery). In a proof-of-concept study, the surface-enhanced Raman scattering and antibacterial performance of the fabricated 3D AgNP@TNA pattern, and the targeted drug delivery for site-specific and high-sensitivity cancer cell assays was investigated.
HubMed – drug

A novel in vitro approach for rapid screening of potential autophagic inductor agents using mammalian cell lines.

Filed under: Drug and Alcohol Rehabilitation

Biotechnol J. 2013 Feb 19;
Martins WK, Severino D, Souza C, Stolf BS, Baptista MS

Recent progress in understanding the molecular basis of autophagy has demonstrated its importance in several areas of human health. However, affordable screening techniques with higher sensitivity and specificity to identify autophagy are needed to move the field forward. In fact, only laborious and/or expensive methodologies such as electron microscopy, dye-staining of autophagic vesicles and LC3-II immunoblotting or immunoassaying are available for autophagy identification. Aiming to fulfill this technical gap, we described here the association of three widely used assays to determine cell viability – CVS (crystal violet staining), MTT reduction (3-[4, 5-dimethylthiaolyl]-2, 5-diphenyl-tetrazolium bromide) and NRU (neutral red uptake) – to predict autophagic cell death in vitro. The conceptual framework of the method is the superior uptake of NR in cells engaging in autophagy. NRU was then weighted by the average of MTT reduction and CVS allowing the calculation of AAU (autophagic arbitrary units), a numeric variable that correlated specifically with the autophagic cell death. The proposed strategy is very useful for drug discovery, allowing the investigation of potential autophagic inductor agents through a rapid screening using mammalian cell lines B16-F10, HaCaT, HeLa, MES-SA and MES-SA/Dx5 in a unique single microplate.
HubMed – drug

Determination of PF-04620110, a novel inhibitor of diacylglycerol acyltransferase-1, in rat plasma using liquid chromatography-tandem mass spectrometry and its application in pharmacokinetic studies.

Filed under: Drug and Alcohol Rehabilitation

Biomed Chromatogr. 2013 Feb 19;
Lee KR, Choi SH, Song JS, Seo H, Chae YJ, Cho HE, Ahn JH, Ahn SH, Bae MA

In this study, we developed a method for the determination of PF-04620110 (2-{(1r,4r)-4-[4-(4-amino-5-oxo-7,8-dihydropyrimido[5,4-f][1,4]oxazepin-6(5H)-yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT-1) inhibitor, in rat plasma and validated it using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC-MS/MS system for quantification. PF-04620110 and imipramine (internal standard) were separated using a Hypersil Gold C(18) column, with a mixture of acetonitrile and 10?mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive-ion mode [M?+?H](+) of multiple-reaction monitoring were m/z 397.0???260.2 for PF-04620110 and m/z 280.8???86.0 for imipramine. The detector response was specific and linear for PF-04620110 at concentrations within the range 0.05-50?µg/mL and the signal-to-noise ratios for the samples were ?10. The intra- and inter-day precision and accuracy of the method matched the acceptance criteria for assay validation. PF-04620110 was stable under various processing and/or handling conditions. PF-04620110 concentrations in the rat plasma samples could be measured up to 24?h after intravenous or oral administration of PF-04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd.
HubMed – drug

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