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排序方式: 共有259条查询结果,搜索用时 15 毫秒
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Application of a radiotelemetric system to evaluate the performance of enteric coated and plain aspirin tablets 总被引:1,自引:0,他引:1
The bioavailability of enteric coated and plain aspirin tablets was studied in four beagle dogs. Blood sampling for enteric coated tablets was planned with the aid of a radiotelemetric system. The release of aspirin from its dosage form was detected by monitoring the change in intestinal pH. Aspirin and salicylic acid levels in plasma obtained from the enteric coated dosage form exhibited familiar concentration versus time absorption profiles. Variation in the plasma concentrations of these two compounds within each dog studied (four runs each) was relatively small when time zero was adjusted to the commencement of tablet dissolution. The plasma levels obtained from plain aspirin (three runs each), however, show atypical absorption. The estimated absolute bioavailability was 0.432 +/- 0.0213 and 0.527 +/- 0.0260 for enteric coated and plain aspirin, respectively. Other pharmacokinetic parameters for these two dosage forms such as the highest observed plasma concentration (Cmax) (10.9 +/- 0.535 microgram/mL versus 13.6 +/- 1.88 micrograms/mL) and the time to reach Cmax (tmax) (26.6 +/- 1.94 min versus 31.0 +/- 7.04 min) agree well. The mean values for gastric emptying time, in vivo coating dissolution time, and in vivo disintegration/dissolution time of the tablet core for enteric coated aspirin are 48.7 +/- 7.23 min, 44.3 +/- 3.80 min, and 34.7 +/- 2.04 min, respectively. 相似文献
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Han HK Rhie JK Oh DM Saito G Hsu CP Stewart BH Amidon GL 《Journal of pharmaceutical sciences》1999,88(3):347-350
The present study characterized Chinese hamster ovary cells overexpressing a human intestinal peptide transporter, CHO/hPEPT1 cells, as an in vitro model for peptidomimetic drugs. The kinetic parameters of Gly-Sar uptake were determined in three different cell culture systems such as untransfected CHO cells (CHO-K1), transfected CHO cells (CHO/hPEPT1) and Caco-2 cells. Vmax in CHO/hPEPT1 cells was approximately 3-fold higher than those in Caco-2 cells and CHO-K1 cells, while Km values were similar in all cases. The uptake of beta-lactam antibiotics in CHO/hPEPT1 cells was three to twelve fold higher than that in CHO-K1 cells, indicating that CHO/hPEPT1 cells significantly enhanced the peptide transport activity. However, amino acid drugs also exhibited high cellular uptake in both CHO-K1 and CHO/hPEPT1 cells due to the high background level of amino acid transporters. Thus, cellular uptake study in CHO/hPEPT1 cells is not sensitive enough to distinguish the peptidyl drugs from amino acid drugs. The potential of CHO/hPEPT1 cells as an in vitro model for peptidomimetic drugs was also examined through the inhibition study on Gly-Sar uptake. Peptidomimetic drugs such as beta-lactam antibiotics and enalapril significantly inhibited Gly-Sar uptake whereas the nonpeptidyl compounds, L-dopa and alpha-methyldopa, did not compete with Gly-Sar for cellular uptake within the therapeutic concentrations. In conclusion, the present study demonstrates the further characterization of CHO/hPEPT1 cells as an uptake model as well as inhibition study and suggests their utility as an alternative in vitro model for drug candidates targeting the hPEPT1 transporter. 相似文献
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Cardiogenic shock (CGS) occurs in 3 to 20% of patients presenting with acute myocardial infarction (MI), and it generally involves dysfunction of at least 40% of the total myocardial mass. Prior to the advent of balloon angioplasty and thrombolysis, in-hospital mortality was greater than 75%. This mortality rate has been consistent in reported series despite the advent of cardiac intensive care units, vasopressor, inotropic, and vasodilator therapy. Intra-aortic balloon counterpulsation therapy provides hemodynamic improvement, and it may provide some mortality benefit when used in conjunction with appropriate revascularization. Survival studies have shown that patency of the infarct-related artery is a strong predictor of survival. No randomized trials have been completed to examine which reperfusion therapy best treats this emergent situation. Subgroup analysis of large scale, multicenter trials, although underpowered, has shown no improvement in mortality with use of thrombolytic agents, leading many to advise use of mechanical intervention. In patients who present with acute MI with contraindications to thrombolysis, primary angioplasty is the treatment of choice. At selected centers, primary angioplasty is comparable to or better than thrombolytic therapy for patients presenting with acute MI, with or without CGS. Studies examining angioplasty in patients with CGS have shown high procedural success rates (75%) and reduced in-hospital mortality (44%), particularly in those patients with successful revascularization. Emergency bypass surgery may improve survival, but it is costly, unavailable to many, and often leads to excessive delays in therapy. If available, we believe that primary angioplasty is the treatment of choice for patients with CGS. 相似文献
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For almost a half century scientists have striven to develop a theoretical model capable of predicting oral drug absorption in humans. From the pH-partition hypothesis to the compartmental absorption and transit (CAT) model, various qualitative/quantitative approaches have been proposed, revised and extended. In this review, these models are classified into three categories; quasi-equilibrium models, steady-state models and dynamic models. The quasi-equilibrium models include the pH-partition hypothesis and the absorption potential concept, the steady-state models include the film model and the mass balance approaches, and the dynamic models include the dispersion, mixing tank and CAT models. The quasi-equilibrium models generally provide a basic guideline for understanding drug absorption trends. The steady-state models can be used to estimate the fraction of dose absorbed. The dynamic models predict both the fraction of dose absorbed and the rate of drug absorption and can be related to pharmacokinetic models to evaluate plasma concentration profiles. 相似文献
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The absorption mechanism of several penicillins was characterized using in situ single-pass intestinal perfusion in the rat. The intrinsic membrane parameters were determined using a modified boundary layer model (fitted value +/- S.E.): Jmax* = 11.78 +/- 1.88 mM, Km = 15.80 +/- 2.92 mM, Pm* = 0, Pc* = 0.75 +/- 0.04 for ampicillin; Jmax* = 0.044 +/- 0.018 mM, Km = 0.058 +/- 0.026 mM, Pm* = 0.558 +/- 0.051, Pc* = 0.757 +/- 0.088 for amoxicillin; and Jmax* = 16.30 +/- 3.40 mM, Km = 14.00 +/- 3.30 mM, Pm* = 0, Pc* = 1.14 +/- 0.05 for cyclacillin. All of the aminopenicillins studied demonstrated saturable absorption kinetics as indicated by their concentration-dependent wall permeabilities. Inhibition studies were performed to confirm the existence of a nonpassive absorption mechanism. The intrinsic wall permeability (Pw*) of 0.01 mM ampicillin was significantly lowered by 1 mM amoxicillin and the Pw* of 0.01 mM amoxicillin was reduced by 2 mM cephradine consistent with competitive inhibition. 相似文献
8.
Structural Specificity of Mucosal-Cell Transport and Metabolism of Peptide Drugs: Implication for Oral Peptide Drug Delivery 总被引:1,自引:0,他引:1
The brush border membrane of intestinal mucosal cells contains a peptide carrier system with rather broad substrate specificity and various endo- and exopeptidase activities. Small peptide (di-/ tripeptide)-type drugs with or without an N-terminal -amino group, including -lactam antibiotics and angiotensin-converting enzyme (ACE) inhibitors, are transported by the peptide transporter. Poly-peptide drugs are hydrolyzed by brush border membrane proteolytic enzymes to di-/tripeptides and amino acids. Therefore, while the intestinal brush border membrane has a carrier system facilitating the absorption of di-/tripeptide drugs, it is a major barrier limiting oral availability of polypeptide drugs. In this paper, the specificity of peptide transport and metabolism in the intestinal brush border membrane is reviewed. 相似文献
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Raman Iyer Shridhar Hegde Yu-E. Zhang James Dinunzio Dharmendra Singhal A. Malick Gregory Amidon 《Journal of pharmaceutical sciences》2013,102(10):3604-3613
The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (Hd) were determined along with Hiestand indices using compacts prepared at a solid fraction of ~0.85. HPMCAS and copovidone exhibited lower Hd, lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher Hd. Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BId) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development. 相似文献