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21.
Dose-dependent pharmacokinetics of probenecid in the rat 总被引:1,自引:0,他引:1
The basic pharmacokinetics of probenecid was studied by administration of three different i.v. bolus doses (50, 75, and 100 mg kg-1) to rats. The protein binding of probenecid in pooled rat serum was estimated by equilibrium dialysis. The unbound fraction was found to increase non-linearly with increasing total concentration, yielding a maximum free fraction of 49 per cent. The plasma concentration data obtained were described by a two-compartment model with Michaelis-Menten elimination. The maximal rate of elimination (Vm) remained unchanged between different doses irrespective of whether it was calculated in total or free concentrations (mean 187.2 +/- 8.3 (SD) microgram min-1). The Michaelis-Menten constant (Km) decreased slightly with increasing dose, while the unbound Michaelis-Menten constant (Km,u) did not change between the doses (mean 37.1 +/- 1.3 (SD) microgram ml-1). The volume of distribution of the central compartment (Vc) did not alter when the dose was increased from 50 to 100 mg kg-1 (mean 56.5 +/- 4.3 (SD) ml), but the unbound volume of distribution of the central compartment (Vc,u) decreased from 186.5 +/- 15.6 (SD) to 89.8 +/- 6.9 (SD) ml, which is in accordance with the reduction to be expected for drugs that only distribute in the extracellular fluid. 相似文献
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Storey RF Becker RC Harrington RA Husted S James SK Cools F Steg PG Khurmi NS Emanuelsson H Lim ST Cannon CP Katus HA Wallentin L 《The American journal of cardiology》2011,(11):1542-1546
The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor reduced the risk for cardiovascular events in patients with acute coronary syndromes compared to clopidogrel but was associated with increased incidence of dyspnea. This substudy assessed whether ticagrelor affects pulmonary function in patients with acute coronary syndromes: 199 patients enrolled in the PLATO trial and receiving randomized treatment with ticagrelor 90 mg twice daily (n = 101) or clopidogrel 75 mg/day (n = 98) took part in the pulmonary function substudy. Patients with advanced lung disease, congestive heart failure, or coronary artery bypass graft surgery after the index event were excluded. Pulse oximetry (blood oxygen saturation), spirometry (forced expiratory volume in 1 second, forced vital capacity, and forced expiratory flow between 25% and 75% of forced vital capacity before and 20 minutes after inhalation of a β(2) agonist), lung volumes (total lung capacity, functional residual capacity, residual volume), and diffusion capacity were performed after patients received study medication for 30 to 40 days. Tests were then repeated <10 days before and approximately 30 days after the discontinuation of study medication. After a mean treatment duration of 31 days, there were no differences between the groups for any of the pulmonary function parameters. At the end of treatment (mean 211 days) and after the discontinuation of study medication (mean 32 days after the last dose), there was also no evidence of a change in pulmonary function in either group. For example, forced expiratory volume in 1 second values before β(2) agonist inhalation in the ticagrelor and clopidogrel groups were 2.81 ± 0.73 and 2.70 ± 0.84 L, respectively, at the first visit and did not change significantly at subsequent visits. In conclusion, no effect of ticagrelor on pulmonary function was seen in this cohort of patients with acute coronary syndromes compared to clopidogrel. 相似文献
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The effect of the direct platelet P2Y12 receptor inhibitor, AR-C69931MX, on activation of blood induced by stents with and without heparin coating was investigated using a whole blood Chandler loop model in vitro. Stents were deployed in Chandler loops. Fresh human blood with heparin and AR-C69931MX was rotated for 1 h at 37 degrees C and used for measurements of platelets, microparticles, thrombin-antithrombin complex (TAT), fibrinogen binding to platelets, P-selectin expression by platelets, CD11b, Prothrombin Fragment F1+2, FXIa-AT, FXIIa-AT, C3a, sC5b-9 and stent score. In the first experiment there were four study groups with unmodified stents: 1a, no AR-C69931MX; 1b, 250 nmol/L; 1c, 750 nmol/L; 1d, 2250 nmol/L of AR-C69931MX. In the second experiment the concentration of AR-C69931MX was 500 nmol/L: 2a; tubings without stent; 2b; tubings with heparin-coated stent; 2c; tubings with unmodified stents. Heparin-coated stents were used in the third experiment: 3a; no AR-C69931MX; 3b; 500 nmol/L of AR-C69931MX. In the first experiment there were significant differences in all parameters analysed except for C3a, and stent score when the group with no AR-C69931MX was compared to all the groups with AR-C69931MX. In the second experiment there were significant differences in platelet count, TAT, FXIa-AT, FXIIa-AT and stent score when unmodified stents were compared to loops with no stents and partly to loops with heparin-coated stents. In the third experiment there was a significant reduction in generation of TAT, stent score and better preservation of platelet number by combining the platelet inhibitor and heparin-coated stents as compared to heparin-coated stents alone. The conclusion is that the direct P2Y12 receptor inhibitor AR-C69931MX reduced the different aspects of activation of blood induced by both unmodified and heparin-coated stents. 相似文献
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Hyaluronan is known to accumulate in tissues during inflammatory diseases associated with graft implantation and rejection of organ allografts. The aim was to evaluate whether hyaluronidase treatment affected hyaluronan content and blood perfusion in graft pancreatitis. Syngeneic rat pancreatic-duodenal transplantations were performed. Two days later blood flow measurements were made with a microsphere technique in both grafted and endogenous pancreas in animals treated with daily injections of vehicle or hyaluronidase (20.000 U/kg). Non-transplanted rats served as controls. Also, samples for analysis of hyaluronan and water content were taken. The hyaluronan content of the pancreatic graft was increased after transplantation. Hyaluronidase treatment markedly reduced total pancreatic and islet blood flow in both grafted and endogenous pancreas, whereas duodenum blood flow was unaffected. No blood flow effects were seen in non-transplanted control rats. Hyaluronan content was increased in the grafted pancreas, but hyaluronidase treatment decreased it to levels comparable to those of the endogenous gland. There were no differences in hyaluronan content in the endogenous pancreases of transplanted and non-transplanted rats. Graft pancreatitis after rat pancreas transplantation is associated with an increased hyaluronan content, which can be reduced by treatment with hyaluronidase. Hyaluronidase treatment of the graft recipients effected a 50% reduction in total pancreatic and islet blood flow in the graft, as well as in the endogenous pancreas. The functional importance of this is at present unknown. 相似文献
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Mohammadi S Esposito M Hall J Emanuelsson L Krozer A Thomsen P 《Clinical implant dentistry and related research》2003,5(4):241-253
Background: It has been suggested that calcium phosphate (CaP) coatings initiate faster bone growth around implants. A major concern about the viable use of these coatings has been their biologic performance related to the coating characteristics. Purpose: The purpose of this study was to investigate the early bone response to micron‐ and submicron‐thick hydroxya‐patite (HA) coatings in cortical and trabecular bone. Materials and Methods: CaP coatings were manufactured by magnetron sputtering. Heat treatment was subsequently used to increase the crystallinity of the coatings. Coatings were characterized by x‐ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma optical emission spectroscopy (ICP‐OES), and stylus profilometry. Four types of CaP‐coated implants were used (0.1 urn and 2.0 μm amorphous; 0.1 um and 2.0 μn crystalline); uncoated machined commercially pure titanium implants served as controls. Four hundred eighty implants were randomly placed in 60 rabbits. Ten animals were followed up for 1 week, 10 for 3 weeks, and 40 for 6 weeks. The bone response was histomorphometrically evaluated. Results: Coatings with a CaP ratio very close to that of HA were produced. Crystalline coatings significantly improved the early bone‐implant contact whereas the amorphous‐coated implants behaved similarly to uncoated titanium. Conclusions: Crystalline CaP coatings 100 nm thick on titanium implants elicited an improved early bone response compared with that of uncoated titanium implants. No further improvement in the bone response was observed with 2 μm coatings. 相似文献
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The aim of this study was to evaluate the consistency of the prevalence of mutans streptococci in a group of Swedish families. Eleven families, which had previously been examined for genotypes of mutans streptococci, were re-examined after 2-5 years. The families consisted of mother, father and a child (mean age 7.2 years at the follow-up examination). One father did not participate. Pooled plaque samples were obtained from buccal and occlusal surfaces. Isolates of mutans streptococci were genotyped using chromosomal DNA digested with restriction endonuclease HaeIII, separated by gel electrophoresis and visualised through UV illumination after ethidium bromide staining. Comparing the DNA fingerprints of mutans streptococci found at baseline and follow-up, 9 children harboured one or two genotypes which were similar on the two sampling occasions. Two of these children had also gained a genotype. The remaining 2 children had lost a genotype each and 1 of them had gained two new genotypes. All 21 adults showed one or two genotypes identical to those found at baseline. Nine of these 21 adults had also lost one genotype. Four of these 9 and additionally 4 of the remaining adults showed one or two new genotypes. Six mother-child pairs shared a genotype at baseline and this pattern remained for five pairs at the end of the study. The results suggest that genotypes of mutans streptococci have a fairly high degree of consistency in children between 3 and 8 years of age as well as in adults, indicating persistence of the strains. However, the results also indicate that some subjects may gain and/or lose genotypes. 相似文献
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