Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
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Currently, there are five anti-Alzheimer's disease drugs approved. These are tacrine, donepezil, rivastigmine, galantamine, and memantine. The mechanism of the first four drugs is acetylcholinesterase inhibition, while memantine is an NMDA-receptor antagonist. ⋯ Therefore, development of the next anti-Alzheimer's disease drug is based on the beta-amyloid theory. We are now studying natural products, such as mulberry leaf extracts and curcumin derivatives, as potential cure for Alzheimer's disease. In this report, we describe some data about these natural products and derivatives.
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TRP channels are well recognized for their contributions to sensory transduction, responding to a wide variety of stimuli including temperature, nociceptive stimuli, touch, osmolarity and pheromones. In particular, the involvement of TRP channels in nociception has been extensively studied following the cloning of the capsaicin receptor, TRPV1. Painful diabetic peripheral neuropathy is described as a superficial burning pain, and it is one of the most commonly encountered neuropathic pain syndromes in clinical practice. ⋯ In addition, intracellular alkalization activated TRPA1 at the whole-cell level, and single-channel openings were observed in the inside-out configuration. Furthermore, intraplantar injection of ammonium chloride into the mouse hind paw caused pain-related behaviors, which were not observed in TRPA1-deficient mice. These results suggest that alkaline pH causes pain sensation through activation of TRPA1.
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Doripenem pharmacokinetics in critically ill patients receiving continuous hemodiafiltration (CHDF).
Objectives of the prospective, open-label study were to investigate pharmacokinetics of doripenem and determine appropriate doripenem regimens during continuous hemodiafiltration (CHDF) in critically ill patients with renal failure (creatinine clearance <30 ml/min) in the intensive care unit at a university hospital in Japan. Six patients received intravenous (IV) administration of 250 mg of doripenem every 12 or 24 hours during CHDF (dialysis rate, 500 ml/h; hemofiltration rate, 300 ml/h) via a polysulfone hemofilter. Doripenem concentrations in pre- and post-membrane blood (plasma) samples collected at specified times during one dosing interval were measured in order to calculate pharmacokinetic parameters and clearance via hemodiafiltration. ⋯ An IV dose of 250 mg of doripenem every 12 hours during CHDF provided adequate plasma concentrations for critically ill patients with renal failure, without resulting in accumulation upon steady-state. Thus, under the conditions tested, CHDF appeared to have little effect on doripenem clearance. Therefore, the blood level of doripenem can be satisfactorily controlled by adjustment of doripenem dose and dosing interval, in accordance with residual renal function in patients receiving CHDF.
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The purpose of this study was to evaluate the incompatibility of ceftriaxone sodium with calcium-containing products using the ionic product of precipitation, and the measurement of insoluble microparticles using a light obscuration particle counter. Appropriate volumes of 2% (w/v) calcium chloride solution were added to 0.4-2 mg/ml ceftriaxone isotonic sodium chloride solution, to make solutions with a final calcium ion concentration of 1.25 mmol/l. The solutions were gently agitated and stored at 37 degrees C for 24 h. ⋯ The numbers of insoluble microparticles in sample solutions made by adding calcium chloride to the sample were significantly higher than those made by adding calcium gluconate. These results suggest that ceftriaxone should not be co-administered with calcium-containing products even if no precipitation is observed visually. There will still be insoluble microparticles caused by incompatibility in the sample solution when the Saturation Index of the solution is over 1.0.
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The purpose of this study was to evaluate the incompatibility of ceftriaxone with calcium-containing products, which had been the subject of an ALERT issued by the FDA. The influence of calcium ion concentration, storage temperature and shaking on the appearance and quantity of insoluble microparticles in mixtures of the two was examined using a light obscuration particle counter and a stereomicroscope. Appropriate volumes of 2% (w/v) calcium chloride solution were added to ceftriaxone sodium for injection (10 mg/ml) to make solutions with final calcium ion concentrations of 0.5-2.5 mmol/l, and stored at 20 degrees C, 25 degrees C, or 30 degrees C. ⋯ The number of microparticles was also significantly increased by shaking. The number of microparticles in mixtures containing 1000 microg/ml ceftriaxone was significantly increased, even though concentrations of calcium ion was 1.25 mmol/l. Overall, not only calcium ion concentration, but storage temperature and shaking affected the extent of precipitation of ceftriaxone with calcium.