Pharmazie
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A pharmacokinetic study of simvastatin (single oral dose, 40 mg) was conducted in 17 healthy Chinese volunteers. Plasma concentrations of simvastatin were determined by an LC-ESI-MS-MS method. The pharmacokinetic parameters of simvastatin were derived with a non-compartmental method. ⋯ We conclude here that there is a small inter-subject variation in simvastatin pharmacokinetics in healthy Chinese volunteers. P-gp, OATP1 B1 and BCRP seem unlikely to play an important role in the pharmacokinetics of simvastatin. The gene-dose effects of ABCG2 c.421 C > A and CYP3A5*3 g.6986A > G on simvastatin pharmacokinetics are not strong enough in Chinese subjects.
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Comparative Study
Clinical efficacy of two forms of intravenous iron--saccharated ferric oxide and cideferron--for iron deficiency anemia.
Over 90% of iron deficiency anemia cases are due to iron deficiency associated with depletion of stored iron or inadequate intake. Parenteral iron supplementation is an important part of the management of anemia, and some kinds of intravenous iron are used. However, few studies have evaluated the clinical efficacy of these drugs. ⋯ Age and sex did not affect improvement of Hb value. CF is fast acting and highly effective compared with SFO for the treatment of iron deficiency anemia. The use of CF may shorten a therapeutic period for iron deficiency anemia, and CF may be feasible for reducing the hospitalization period.
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The drugs that are currently used to treat pulmonary hypertension (PH) lack the ability to inhibit or reverse the pulmonary vascular remodeling that occurs during the course of the disease. We propose a novel method that combines the therapeutic powers of the potassium channel opener pinacidil and the statin drug simvastatin. These two drugs do not share similar mechanisms of treating PH. ⋯ We found that levels of mPAP, right ventricle Fulton index, pulmonary arteriolar wall thickness and muscularization, cell growth rate, transforming growth factor beta (TGF-beta), lung tissue matrix metalloproteinase-2 (MMP-2), MMP-9 and lung tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), vascular smooth muscle cell (VSMC) contractile protein SM-alpha-actin, and SM-alpha-actin mRNA of these different groups were all significantly lower in the combination-treated group than in the untreated group. Subjects in the combination-treated group also showed lower levels than those in either the pinacidil-treated or simvastatin-treated group. These results support our hypothesis and provide basis for a new, more effective therapeutic methods of treating PAH in human patients.
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Cardiac myofibroblast differentiation, characterized by expression of alpha-smooth muscle actin (alpha-SMA) and fibrillar collagens, plays a key role in the adverse myocardial remodeling. Fluorofenidone (1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone, AKF-PD) is a novel pyridone antifibrotic agent, which exerts a strong antifibrotic effect. This study investigated the potential role of AKF-PD in suppressing cardiac myofibroblast conversion induced by transforming growth factor-beta1 (TGF-beta1) and the related mitogen-activated protein kinase (MAPK) signaling pathways in neonatal rat cardiac fibroblasts. ⋯ In addition, AKF-PD, PD98059 and SB203580 greatly attenuated alpha-SMA expression induced by TGF-beta1. Furthermore, AKF-PD significantly blocked TGF-beta1-induced phosphorylation of ERK. These results indicate that (1) AKF-PD inhibits TGF-beta1-induced myofibroblast differentiation; (2) the anti-fibrotic effects of AKF-PD are partially mediated by ERK phosphorylation.
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Continuous amoxicillin infusion for deep infection's intravenous treatment is performed using elastomeric portable pumps carried under clothing and requires high doses of antibiotic. Therefore, we evaluated the stability of amoxicillin in those medical devices, with particular focus on both drug concentration and storage temperature. Stability of 20, 40, and 60g/L amoxicillin solutions in 300 mL portable pumps stored at 20 or 35 degrees C was studied by visual examination and drug concentration measurements at T0; T0 + 12 h; T0 + 24 h and; T0 + 48 h. ⋯ This degradation process was amplified at T0 + 48 h, with degradation rates of 37 and 42% at 20 and 35 degrees C, respectively. Stability of amoxicillin in pump is guarantied over 48 h up to concentrations of 40 g/L. At 60 g/L major degradation of the antibiotic was observed.