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911.
本文报告了氟卡胺血药浓度的高效液相色谱测定法。以氟基安定为内标,以含有离子对试剂的甲醇—水溶液为流动相,建立了测定条件。绘制标准曲线得回归方程为Y=0.0017X+0.0131,r=0.9975。氟卡胺及内标的回收率均大于94%,日内及日间变异系数均小于5%。正常人口服氟卡胺后的药代动力学参数,Ka=0.908h-1,T1/2K=8.131h,TPK=3.487h,AUC=441.8ng.h/ml。病人口服氟卡胺的有效血浓度为423.64±227.4ng/ml。 相似文献
912.
913.
Hiram C Polk Talmadge A Bowden Layton F Rikkers Charles M Balch Claude H Organ John A Murie Walter J Pories Marcus W Buechler John P Neoptolemos Victor W Faxio Seymour I Schwartz John L Cameron Keith A Kelly Jay L Grosfeld David W McFadden Wiley W Souba Basil A Pruitt K Wayne Johnson Robert B Rutherford Maurice E Arregui Carol E H Scott-Conner Andrew L Warshaw Michael G Sarr Alfred Cuschieri Bruce V MacFadyen Ronald K Tompkins 《Journal of gastrointestinal surgery》2002,6(3):512-513
914.
Metabolism of digoxin, digoxigenin digitoxosides and digoxigenin in human hepatocytes and liver microsomes 总被引:2,自引:0,他引:2
B. Lacarelle R. Rahmani G. de Sousa A. Durand M. Placidi and JP Cano 《Fundamental & clinical pharmacology》1991,5(7):567-582
In vitro metabolism of digoxin and its cleavage-related compounds was investigated using hepatocytes in primary culture and microsomal fractions both isolated from human livers. On these models, digoxin (DG3) and digoxigenin bisdigitoxoside (DG2) were not shown to be significantly metabolized in vitro in man. Therefore, it appeared that the stepwise cleavage of DG3 and DG2 sugars was not cytochrome P450 dependent. This enzymatic system probably plays a minor role in humans for this particular reaction. However, digoxigenin monodigitoxoside (DG1) and digoxigenin (DG0) which are known to be formed after intra-gastric hydrolysis of DG3, were extensively converted to polar compounds (mainly glucuronides). In addition, using human liver microsomes, a wide variability in UDP-glucuronyl transferase (UDPGT) activities responsible for DG1 glucuronidation was demonstrated. These results suggest that two main factors may contribute to the overall interindividual variability of digoxin biotransformation: 1), the individual intra-gastric pH which influences the sugar cleavage leading to DG1 and DG0; ii), a variability in the level of the hepatic UDPGT specific for digitalis compounds conjugation. 相似文献
915.
L. Hary A. Smail JP Ducroix J. Baillet and M. Andrejak 《Fundamental & clinical pharmacology》1991,5(9):789-795
The pharmacokinetics of piperacillin were evaluated in seven healthy volunteers, eight cirrhotic patients without ascites and 11 cirrhotic patients with sterile ascites after a single 15-min intravenous infusion of 4 g of the drug. In ascitic patients, piperacillin rapidly entered the peritoneal fluid. Peritoneal concentrations were higher than 10 mg/l from 0.5 to 8 h after the infusion. Disappearance rate of piperacillin was slower in the ascitic fluid than in plasma. The plasma half life of piperacillin was more prolonged in cirrhotic patients that in control subjects. This difference was more marked in ascitic patients for whom half life was twice as high as in volunteers (1.95 versus 0.91 h; P less than 0.01). 相似文献
916.
Lymphocyte subsets in a group of intensely transfused (greater than 10 units/year) patients on long-term hemodialysis were compared with those in a carefully controlled population of lightly transfused (1-10 units/year, no units during study period) long-term dialysis patients. The data confirm previous reports of lymphopenia and a symmetrical reduction of both T- and B-cell subpopulations in patients on long-term dialysis. Eleven (36.7%) of 30 intensely transfused dialysis (ITD) patients had a low T8 population when expressed as a percentage value, while 0 of 25 lightly transfused dialysis (LTD) control patients exhibited a low percentage of T8 cells. There were no significant absolute differences between the lymphocyte subsets in the ITD and LTD patients. These data contrast with previous reports of other groups of ITD patients in whom there was an observed increase in T8 cytotoxic suppressor cells. Our findings suggest that the immunologic effects of renal failure and long-term dialysis largely override the increase in T8 lymphocyte subsets observed in other groups of transfused patients. There is little difference between ITD and LTD patients, but both groups are significantly different from nontransfused controls. Further longitudinal studies are needed in completely untransfused patients to resolve the contribution of minimal transfusion therapy to the immunologic deficits observed in long-term dialysis patients. 相似文献
917.
918.
P Riant F Bree S Urien C Hamberger E Albengres and JP Tillement 《Fundamental & clinical pharmacology》1990,4(1):105-114
Sodium valproate (VPA) is a drug widely used in the treatment of epileptics often in association with benzodiazepines. Recent animal studies have shown that the addition of valproate increases diazepam levels in the cortex and the cerebellum (Hariton et al, 1985). The aim of our study was to determine the effect of VPA on the transfer of benzodiazepines through the blood-brain barrier. They were investigated using the intracarotid injection technique in rats as described by Oldendorf (1971). Our results show that the 14C-chlordiazepoxide brain extraction is significantly higher in rats on prolonged valproate treatment than in controls. With regard to plasma protein binding effects on chlordiazepoxide transport, our data indicate that a fraction of the protein-bound chlordiazepoxide could transfer from the intracapillary space to the brain tissue space because of enhanced drug dissociation from albumin in the brain microcirculation (Kd in vitro = 74.1 microM; Kd in vivo = 793.7 microM). Two distinct mechanisms can be deduced from this study: 1) chlordiazepoxide is displaced from HSA by valproate, 2) in addition, this fatty acid could increase drug permeation through the blood brain barrier (PS/F (chlordiazepoxide) = 0.60 in controls, PS/F (chlordiazepoxide) = 0.97 in treated rats). On the contrary, the washout of the benzodiazepine from the rat brain does not seem to be modified by the addition of valproate. 相似文献
919.
Activation of the fibrinogen binding site on platelets isolated from a patient with the Strasbourg I variant of Glanzmann's thrombasthenia 总被引:6,自引:4,他引:2
Kouns WC; Steiner B; Kunicki TJ; Moog S; Jutzi J; Jennings LK; Cazenave JP; Lanza F 《Blood》1994,84(4):1108-1115
One proposed ligand binding site on platelet integrin alpha IIb beta 3 is the region of the beta 3 subunit encompassing amino acids 211-221. However, we recently showed that synthetic peptides corresponding to amino acids 211-221 inhibit fibrinogen binding to alpha IIb beta 3 by binding to alpha IIb beta 3 and not to fibrinogen. In this study, we show that AP6, a monoclonal antibody (MoAb) directed against amino acids 214-221 of beta 3, bound to immobilized active alpha IIb beta 3 but did not inhibit fibrinogen binding to the complex. We then determined whether nonfunctional alpha IIb beta 3 on platelets with a beta 3 Arg-214-->Trp mutation (Strasbourg I variant of Glanzmann's thrombasthenia or GTV) could be induced to aggregate after treatment with dithiothreitol (DTT). DTT has been shown to expose the fibrinogen receptor on normal platelets. DTT treatment of GTV platelets did result in the formation of the fibrinogen binding site as indicated by the binding of pI-55, an MoAb that only binds to the activated form of alpha IIb beta 3. Furthermore, DTT-treated GTV platelets aggregated in the presence of fibrinogen and divalent cations. This aggregation was inhibited by EDTA, RGDS, and the selective alpha IIb beta 3 antagonist, Ro 43-5054. These data show that Arg-214 of beta 3 is not required for fibrinogen binding or for platelet aggregation. However, this amino acid appears to be critical for the formation and for the maintenance of the correct tertiary structure of the fibrinogen binding site on alpha IIb beta 3. 相似文献
920.