Pharmaceutical research
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Pharmaceutical research · Jan 2008
Influence of plasma cholesterol and triglyceride concentrations and eritoran (E5564) micelle size on its plasma pharmacokinetics and ex vivo activity following single intravenous bolus dose into healthy female rabbits.
Eritoran (E5564) is a glycophospholipid that acts as a toll-like receptor 4 (TLR4) antagonist that is being tested as a treatment for severe sepsis and septic shock. In the blood, eritoran binds to plasma lipoproteins altering its pharmacokinetic and pharmacodynamic (PD) effects in vivo. The purpose of this study was to determine the influence of changes in plasma cholesterol and triglyceride concentrations on the plasma pharmacokinetics and ex vivo activity of eritoran following single intravenous bolus dosing of eritoran to healthy female rabbits fed either a regular chow diet or a cholesterol-enriched diet. This was done with eritoran administered as stable micelle formulations of mean hydrodynamic diameters of 8 or 27 nm). ⋯ These findings suggest that plasma pharmacokinetics and activity of eritoran maybe influenced by eritoran micelle size and plasma TC and TG concentrations.
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Pharmaceutical research · Aug 2007
In vivo effects of glycyl-glutamate and glycyl-sarcosine on gabapentin oral absorption in rat.
The objective of this study was to evaluate the in vivo consequences of glycyl-glutamate coadministration on gabapentin oral absorption. ⋯ These findings are unique in demonstrating that under physiologic, in vivo conditions, the luminal presence of glycyl-glutamate could dramatically enhance the Cmax and AUC(0-6 h) of gabapentin. The results are consistent with previous in situ intestinal perfusion studies in rat, and establish a functional interaction between the activities of PEPT1 and amino acid exchangers.
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Pharmaceutical research · Jul 2007
Modeling methadone pharmacokinetics in rats in presence of P-glycoprotein inhibitor valspodar.
To quantify the in vivo role of P-glycoprotein (P-gp) in the pharmacokinetics of methadone after intravenous and oral administration, using valspodar as a P-gp inhibitor. ⋯ Valspodar increased methadone's bioavailability as consequence of P-gp inhibition, which resulted in an increased analgesic effect of methadone.
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Pharmaceutical research · Jul 2007
Comparative StudyProline prodrug of melphalan targeted to prolidase, a prodrug activating enzyme overexpressed in melanoma.
To determine the bioactivation and uptake of prolidase-targeted proline prodrugs of melphalan in six cancer cell lines with variable prolidase expression and to evaluate prolidase-dependence of prodrug cytotoxicity in the cell lines compared to that of the parent drug, melphalan. ⋯ The data corroborates the specificity of prophalan-L: activation by prolidase as well as prolidase-targeted cytotoxicity of prophalan-L: in cancer cell lines. Hence, prophalan-L: , a stable prodrug of melphalan, exhibits potential for efficiently targeting melanoma with reduced systemic toxicity.
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Pharmaceutical research · May 2007
ReviewNew insights into the pathogenesis and treatment of idiopathic pulmonary fibrosis: a potential role for stem cells in the lung parenchyma and implications for therapy.
Idiopathic Pulmonary Fibrosis (IPF) is a chronic, progressive, and often fatal form of interstitial lung disease. It is characterized by injury with loss of lung epithelial cells and abnormal tissue repair, resulting in replacement of normal functional tissue, abnormal accumulation of fibroblasts and myofibroblasts, deposition of extracellular matrix, and distortion of lung architecture which results in respiratory failure. Despite improvements in the diagnostic approach to IPF and active research in recent years, the molecular mechanisms of the disease remain poorly understood. ⋯ Gender mismatched bone marrow or lung transplant recipients serve as natural populations in which to study the role of bone marrow-derived stem cells in recovery from pulmonary diseases. Understanding the mechanism of recruitment of stem cells to sites of injury, and their involvement in tissue repair, regeneration, and remodeling may offer a novel therapeutic target for developing more effective treatments against this fatal disorder. This article reviews the new concepts in the pathogenesis, current and future treatment options of pulmonary fibrosis, and the recent advances regarding the roles of stem cells in lung tissue repair, regeneration, and remodeling.