Current Issue : July - September Volume : 2017 Issue Number : 3 Articles : 5 Articles
Hemoglobin (Hb) is an ideal material for use in the development of an oxygen carrier\nin view of its innate biological properties. However, the vascular retention of free Hb is too short\nto permit a full therapeutic effect because Hb is rapidly cleared from the kidney via glomerular\nfiltration or from the liver via the haptogloblin-CD 163 pathway when free Hb is administered in\nthe blood circulation. Attempts have been made to develop alternate acellular and cellular types\nof Hb based oxygen carriers (HBOCs), in which Hb is processed via various routes in order to\nregulate its pharmacokinetic properties. These HBOCs have been demonstrated to have superior\npharmacokinetic properties including a longer half-life than the Hb molecule in preclinical and\nclinical trials. The present review summarizes and compares the pharmacokinetic properties of\nacellular and cellular type HBOCs that have been developed through different approaches, such as\npolymerization, PEGylation, cross-linking, and encapsulation....
Clopidogrel has significantly reduced the incidence of recurrent atherothrombotic\nevents in patients with acute coronary syndrome (ACS) and in those undergoing percutaneous\ncoronary intervention (PCI). However, recurrence events still remain, which may be partly due to\ninadequate platelet inhibition by standard clopidogrel therapy. Genetic polymorphisms involved\nin clopidogrel�s absorption, metabolism, and the P2Y12 receptor may interfere with its antiplatelet\nactivity. Recent evidence indicated that epigenetic modification may also affect clopidogrel response.\nIn addition, non-genetic factors such as demographics, disease complications, and drug-drug\ninteractions can impair the antiplatelet effect of clopidogrel. The identification of factors contributing\nto the variation in clopidogrel response is needed to improve platelet inhibition and to reduce risk\nfor cardiovascular events. This review encompasses the most recent updates on factors influencing\npharmacokinetic and pharmacodynamic responses to clopidogrel....
Noise-induced hearing loss (NIHL) is a global health problem affecting over 5% of the population worldwide. We have shown\npreviously that acute noise-induced cochlear injury can be ameliorated by administration of drugs acting on adenosine receptors\nin the inner ear, and a selective A1 adenosine receptor agonist adenosine amine congener (ADAC) has emerged as a potentially\neffective treatment for cochlear injury and resulting hearing loss. This study investigated pharmacokinetic properties ofADACin rat\nperilymph after systemic (intravenous) administration using a newly developed liquid chromatography-tandem mass spectrometry\ndetection method. The method was developed and validated in accordance with the USA FDA guidelines including accuracy,\nprecision, specificity, and linearity. Perilymph was sampled from the apical turn of the cochlea to prevent contamination with\nthe cerebrospinal fluid. ADAC was detected in cochlear perilymph within two minutes following intravenous administration and\nremained in perilymph above its minimal effective concentration for at least two hours. The pharmacokinetic pattern of ADAC\nwas significantly altered by exposure to noise, suggesting transient changes in permeability of the blood-labyrinth barrier and/or\ncochlear blood flow. This study supports ADAC development as a potential clinical otological treatment for acute sensorineural\nhearing loss caused by exposure to traumatic noise....
Tuberculosis (TB) treatment is long and complex, typically involving a combination of drugs taken for 6 months. Improved drug regimens to shorten and simplify treatment are urgently required, however a major challenge to TB drug development is the lack of predictive pre-clinical tools. To address this deficiency, we have adopted a new high-content imaging-based approach capable of defining the killing kinetics of first line anti-TB drugs against intracellular Mycobacterium tuberculosis (Mtb) residing inside macrophages. Through use of this pharmacokinetic-pharmacodynamic (PK-PD) approach we demonstrate that the killing dynamics of the intracellular Mtb sub-population is critical to predicting clinical TB treatment duration. Integrated modelling of intracellular Mtb killing alongside conventional extracellular Mtb killing data, generates the biphasic responses typical of those described clinically. Our model supports the hypothesis that the use of higher doses of rifampicin (35�mg/kg) will significantly reduce treatment duration. Our described PK-PD approach offers a much needed decision making tool for the identification and prioritisation of new therapies which have the potential to reduce TB treatment duration....
A simple and sensitive HPLC-UV method has been developed for the simultaneous determination of quercetin, luteolin, and\napigenin in rat plasma after oral administration of Matricaria chamomilla L. extract. The flow rate was set at 1.0ml/min and\nthe detection wavelength was kept at 350 nm. The calibration curves were linear in the range of 0.11ââ?¬â??11.36 ...
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