Journal of pharmaceutical sciences
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The purpose of this study was to evaluate the effectiveness of a novel fluorocarbon-based sevoflurane emulsion in dogs previously shown to produce short-term rodent anesthesia. On the basis of an unexpected allergic-type clinical reaction, we also tested the hypothesis that this type of formulation causes histamine release and complement activation. Physiological parameters, plasma histamine levels (radioimmunoassay), and complement activation (enzyme immunoassay) were quantified in response to emulsion components, including F13M5 (the emulsion's fluorocarbon-based polymer) and methoxy poly(ethylene glycol) 5000 (the polymer's hydrophilic block). ⋯ Direct complement activation by the emulsion or its components was weak or absent. An allergic response leading to histamine release, likely initiated by the F13M5 component via an immunoglobulin pathway, is associated with an intravenous fluorocarbon-based emulsion of sevoflurane. Subsequently, its usefulness in medicine in its present formulation is limited.
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This is a commentary on how the trade-related aspects of intellectual property rights (TRIPS) agreement has impacted India as a supplier of generic antiretrovirals (ARVs). We provide a systematic review of the issues related to the TRIPS agreement that affects India. ⋯ Currently, mechanisms exist for the generic production of almost all ARVs in India, including second-line drugs; however, the manufacture of these drugs by generic pharmaceutical companies may require additional market incentives. Compulsory licensing may emerge as an additional mechanism by which India can provide affordable versions of patented drugs to Least Developed Countries (LDCs).
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Despite its use in commercially available drugs such as intravenous voriconazole, there is little known in the medical literature about the clinical pharmacology of the solubilizing agent, sulfobutylether-beta-cyclodextrin (SBECD). This paper summarizes all known data on SBECD pharmacokinetics and safety. In animals, volume of distribution approximates extracellular water volume and clearance is determined by the glomerular filtration rate. ⋯ SBECD has also been studied in healthy volunteers and subjects with renal dysfunction. Whereas plasma SBECD levels accumulate in those with renal compromise, there were no deleterious effects on renal function. Nonetheless, serum creatinine levels should be monitored in subjects with renal compromise receiving multiple doses of SBECD.
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Randomized Controlled Trial
No clinically relevant pharmacokinetic and safety interactions of ambrisentan in combination with tadalafil in healthy volunteers.
Ambrisentan is a nonsulfonamide, ET(A)-selective endothelin receptor antagonist (ERA) approved for the treatment of pulmonary arterial hypertension (PAH), and tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor under investigation for treatment of PAH. Due to the potential combination use, the pharmacokinetic (PK) interactions between these two drugs were assessed in a crossover study in 26 healthy adults. Single-dose PK of ambrisentan (10 mg) and its metabolite, 4-hydroxymethyl ambrisentan, were determined in the absence and presence of multiple doses of tadalafil (40 mg QD). ⋯ The safety profile of the drugs combined was similar to that of either drug alone. No dose adjustments should be necessary when these drugs are coadministered. These results are in contrast to previous reports that the sulfonamide-based ERA bosentan can cause marked decreases in the exposure of tadalafil.
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Tissue engineering is an emerging multidisciplinary field of investigation focused on the regeneration of diseased or injured tissues through the delivery of appropriate molecular and mechanical signals. Therefore, bone tissue engineering covers all the attempts to reestablish a normal physiology or to speed up healing of bone in all musculoskeletal disorders and injuries that are lashing modern societies. This article attempts to give a pharmaceutical perspective on the production of engineered man-made bone grafts that are described as implantable tissue engineering therapeutics, and to highlight the importance of understanding bone composition and structure, as well as osteogenesis and bone healing processes, to improve the design and development of such implants. In addition, special emphasis is given to pharmaceutical aspects that are frequently minimized, but that, instead, may be useful for formulation developments and in vitro/in vivo correlations.