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101.
Berthe L. F. van Eck-Smit Ernst E. van der Wall Patrick P. A. M. Verhoeven Suzanne Poots Aeilko H. Zwinderman Ernest K. J. Pauwels 《European journal of nuclear medicine and molecular imaging》1996,23(2):188-194
As several reinjection procedures have shown encouraging results in terms of imaging, we investigated whether the kinetics of thallium-201 would differ between the standard stress-redistribution-reinjection approach and the stress-immediate reinjection approach. In 53 consecutive patients with undiagnosed chest pain, 75 MBq (2 mCi)201Tl was injected at maximal exercise. In 26 of these patients (group I), 37 MBq (1 mCi)201Tl was reinjected immediately after completing the exercise images (the immediate reinjection procedure) and in 27 patients (group II), 37 MBq (1 mCi)201Tl was reinjected after completing 3-h redistribution images (the standard reinjection procedure). Mean peak201Tl blood activity after exercise was 17.7±12.5 kBq/ml (4.8±3.4 mCi/ml) for group I versus 16.4±9.2 kBq/ml (4.4±2.5 mCi/ml) for group II (NS). The relative increase in201Tl blood activity after reinjection of half the initial dose [37 MBq (1 mCi)] exceeded 50% of the initial peak in both groups. The relative amount of201Tl delivered to the myocardium was assessed by the area under the curve after both exercise and reinjection, and was 117%±72% for group I and 112%±73% for group II (NS). Blood clearance of201Tl was at least biexponential. Mean early decay constants (1) after exercise and reinjection were 0.30±0.18 min–1 and 0.22±0.046 min–1 respectively for group I (T
1/2 2.3 min and 3.2 min respectively, NS), and 0.30±0.12 min–1 and 0.24±0.07 min–1 respectively for group II (T
1/2 2.3 min and 2.9 min respectively, NS). For both procedures no significant differences were found between 1 after exercise and 1 after injection. The mean late clearance (2) from the blood was 0.032±0.056 min–1 and 0.012±0.012 min–1 respectively for group I (T
1/2 21.6 min and 57.7 min respectively, NS), and 0.036±0.030 min–1 and 0.014±0.014 min–1 respectively for group II (T
1/2 19.3 min and 49.5 min respectively, NS). Also, no significant differences were found between 2 after exercise for both groups and between 2 after reinjection for both groups. We conclude that reinjection of 37 MBq (1 mCi)201Tl (half the initial dose) results in a relative increase in the initial peak and a relative increase in the amount of201Tl delivered to the myocardium of more than 50% for both the standard and the immediate reinjection procedure. The clearance of201Tl from the blood was not influenced by exercise or by the time of reinjection. Based on201Tl kinetics as measured in the peripheral blood, there is no reason to postpone reinjection until 3–4 h following exercise. 相似文献
102.
On-line urea kinetics in haemodiafiltration 总被引:1,自引:1,他引:0
Santoro A.; Tetta C.; Mandolfo S.; Arrigo S.; Berti M.; Colasanti G.; D'Amico G.; Imbasciati E.; Mazzocchi C.; Pacini G.; Spongano M.; Thomaseth K.; Wratten M. L.; Zucchelli P. 《Nephrology, dialysis, transplantation》1996,11(6):1084-1092
BACKGROUND.: Calculation of Kt/V and assessment of nutrition have so farbeen dependent upon off-line urea measurements of blood or dialysatesamples. Here we describe a biosensor for on-line urea measurementduring haemodiafiltration. METHODS.: The biosensor consisted of a cartridge containing covalentlylinked urease placed between two conductivity cells. The biosensorwas placed on the outlet line of a haemofilter in series witha dialyser in order to obtain an aliquot of plasma ultrafiltratefor on-line measurement of urea. RESULTS.: Urea nitrogen concentrations were highly correlated to the difference() in conductivity measured by the two conductivity cells bothin aqueous solutions (in-vitro studies, y=6.676+32.12x,R2=0.998, P<0.0001) and in ultrafiltrates (ex-vivo studies,y=6.7+32.01x, R2=0.98, P<0.00001). conductivity washighly reproducible (% variation: 0.85.3%) and stable(maximal % variation at 150 mg/dl after 180 min: 0.9±0.3vs initial values). The intradialytic plasma water urea profilewas obtained in 10 haemodialysis patients. To study recirculation,the plasma water urea profile was analysed before and 3 minafter stopping the dialysate flow. The pre- and post-stoppedflow ratio (1.21±0.1, mean±1 SD) was superimposableto conventional blood sampling data (opposite arm venous/arterial:1.22±0.11) and allowed correction for recirculation.A novel approach to urea kinetic modelling was described andused to reliably project end-dialysis and post-dialysis reboundurea concentration as early as 90 min. Projected (29.2±10.4g) or measured (29.8±10.5 g) net urea removal was highlycorrelated with the amount of urea collected in the total spentdialysate (29.7±10.6 g) (R2=0.99, R2=0.97 respectively). CONCLUSIONS.: These results indicate that on-line, real-time analysis of ureakinetics may provide information on delivery of adequate dialysisin high-efficiency techniques. 相似文献
103.
Jonas M. Weissbrod Rakesh K. Jain Francis M. Sirotnak 《Journal of pharmacokinetics and pharmacodynamics》1978,6(6):487-503
A lumped compartmental model has been derived to predict methotrexate concentration as a function of time for L1210 cells in BD2F
1
female mice at doses ranging from 3 mg/kg to 400 mg/kg. Using standard methods of parameter estimation as well as experimental determinations, an integrated approach was derived to account for the differences between the subcutaneous (s.c.) and intraperitoneal (i.p.) modes of injection. It was found that a single generalized forcing function can be used to fit plasma concentration after s.c. injection for all doses. Adequate fits (average error<20% while the standard deviation of experimental determinations was±22%) of L1210 cell data after s.c. injection were obtained. The best results were for a maximum facilitated influx constant Vmax
of 0.424 g/min/ml, a Michaelis influx constant Km
of 1,42 g/ml, and a first-order efflux constant of 0.047 min–1.The model simulations were not sensitive to Vmax, Km,and so long as the ratio Vmax/was approximately 9g/ml. The values of V
max
,K
m
,and which were obtained from our analysis of the in vivodata can be explained on the basis of previously performed in vitroexperiments. The parameters obtained from modeling the s.c. data were then applied for i.p. injection data. The resulting fits were adequate (average error<20% while the standard deviation of experimental determinations was±22%). A single generalized forcing function for drug concentration in the peritoneal cavity after i.p. injection for all doses was derived. The application of these results enables the prediction of methotrexate concentration in neoplastic cells at other doses after either s.c. or i.p. injection. 相似文献
104.
Further studies on the extraneuronal uptake and metabolism of isoprenaline in the perfused rat heart
H. Bönisch 《Naunyn-Schmiedeberg's archives of pharmacology》1978,303(2):121-131
Summary To simultaneously determine the kinetics of removal, O-methylation and accumulation of 3H-isoprenaline, isolated rat hearts were perfused for 4 min with various concentrations of 3H-isoprenaline. The apparent K
m
for the O-methylation of 3H-isoprenaline (3.3±0.5 M) was more than one order of magnitude lower than the corresponding value for the accumulation of unchanged amine (71.3±7.1 M). The apparent K
m
for removal was very similar to that for accumulation (63.2±5.9 M). At perfusion concentrations higher than 25 M, i.e. when O-methylation was saturated, removal virtually equalled accumulation. However, at low substrate concentrations removal of 3H-isoprenaline was overwhelmingly followed by O-methylation; this led to a marked difference between rates of removal and those of accumulation.When initial rates of uptake of 3H-isoprenaline were determined after 1.5 min of perfusion of the hearts by the method of Graefe et al. (1978), the uptake of 3H-isoprenaline consisted of two components: a nonsaturable and a saturable (after subtraction of the nonsaturable component from the total uptake).The kinetic constants of the saturable component of uptake were higher than those obtained after 4 min perfusion (see above) (K
m
: 110±19 M; V
max: 80±4 nmoles·g–1·min–1).Corticosterone competitively inhibited the saturable component of uptake of 3H-isoprenaline (K
m
: 1.2 M).During wash out of accumulated 3H-isoprenaline, O-methylation took place predominantly in one of the two extraneuronal compartments. The efflux of 3-O-methyl-3H-isoprenaline (3H-OMI), the O-methylated metabolite of 3H-isoprenaline, was characterized by a half time of about 1.2 min. O-methylation accelerated the loss of radioactivity from the tissue during wash out.The extraneuronal uptake of 3H-isoprenaline was characterized as a pump and leak system by means of steady-state kinetics of accumulation of 3H-isoprenaline. Half saturation of the steady-state accumulation was observed at a concentration of 104.5 ±18.5 M 3H-isoprenaline; the leak component was characterized by a rate constant of 0.0359 min–1.This study was supported by the Deutsche Forschungsge-meinschaftA preliminary account was presented at the 6th International Congress of Pharmacology (Graefe et al., 1975) 相似文献
105.
Summary The steady-state kinetics of chlorophenoxyisobutyric acid (CPIB) and of bezafibrate were investigated in a strictly controlled, randomised cross-over study in 10 female volunteers, after the conventional oral doses of clofibrate 0.5 g and bezafibrate 0.2 g at 8-h intervals. The mean steady-state concentration of CPIB in serum was 34 times higher than that of bezafibrate, which was due to the considerable cumulation of CPIB, whereas no cumulation of bezafibrate was observed. This is supported by comparison of the AUCs, and of the maximum and mean concentrations of bezafibrate after the first and last doses. (0.44 and 0.49 h–1) and the half-lives (1.6 and 1.4 h) were almost identical after the first and last doses of bezafibrate. The median total clearances of CPIB and bezafibrate amounted to 10.5 and 142.5 ml/min, respectively, if complete absorption of both drugs is assumed. Since the apparent volumes of distribution were in the same range for both drugs, the amount of drug present in the organism in steady-state also differed by a factor of approximately 30 under the usual dosage regimen. 相似文献
106.
The Relationship of Diastereomer Hydrolysis Kinetics to Shelf-Life Predictions for Cefuroxime Axetil
Ngoc-Anh T. Nguyen 《Pharmaceutical research》1991,8(7):893-898
Cefuroxime axetil, an ester prodrug of cefuroxime, is comprised of a 50:50 mixture of diastereomers A and B. The first-order hydrolysis kinetics of cefuroxime axetil were investigated as a function of pH, temperature, buffers, and ionic strength. Chromatographically identified hydrolysis products were cefuroxime, 2-cefuroxime axetil, and ,-sulfoxides. Buffer catalysis was observed in acetate and phosphate buffers. No significant kinetic effect was observed for ionic strength in the range µ = 0.1-1.0. The pH–rate profiles for hydrolysis of cefuroxime axetil isomeric mixture were obtained at 45, 35, and 25°C. The equation defining the cefuroxime axetil hydrolysis rate constant as a function of pH was k
obs = k
H(a
H) + k
s + k
OH(K
w/a
H), exhibiting maximal stability in the pH range 3.5 to 5.5. The predicted profile at 5°C was in excellent agreement with experimental data in the pH range 3.6 to 5.5. In the pH range 1 to 9, the maximum difference observed for individual hydrolysis constants of isomers was 27%. Shelf-life estimates based on the hydrolysis rate constants for cefuroxime axetil as an isomeric mixture were shown to be equivalent to those based on individual hydrolysis rate constants for isomers A and B. 相似文献
107.
Sylvie Perreault Huy Ong Patrick du Souich 《Journal of pharmacokinetics and pharmacodynamics》1992,20(5):461-476
This study assessed the influence of dose and route of administration on salbutamol kinetics and hypokaliemic effect. Salbutamol plasma kinetics were studied in a first group of 6 rabbits who received 60, 800, and 60 g/kg by the intravenous (iv), oral (po), and intratracheal (it) routes, respectively, at 1-week intervals. A second group of 6 rabbits received 120, 2400, and 120 g/kg of salbutamol by the same three routes. Multiple blood samples were withdrawn to assay salbutamol and potassium. Following iv salbutamol (60 g/kg), total plasma clearance was 82±5 ml/min per kg, apparent volume of distribution was 5.0±0.5 l/kg, and terminal half- life was 41±2 min. Similar values were estimated when 120 g/kg of salbutamol was administered iv or was given po or it. The bioavailability of po and it salbutamol was approximately 1 and 20%, respectively. For the first group, the maximal decrease in plasma potassium elicited by salbutamol was 0.80±0.19, 0.48±0.22, and 0.78±0.46 mmol/l, and for the second group, maximal decrement was 1.31±0.37, 0.70±0.24, and 0.84±0.17 mmol/l for the iv, po, and it routes, respectively. Compared to salbutamol peak plasma concentrations, maximal decrease in plasma potassium appeared between 60 and 108 min later for the iv route, 90 and 25 min later for po and it routes, and for this reason, the hypokaliemic effect was not associated to salbutamol plasma concentrations. The hypokaliemic effect was dependent upon the route, e.g., po>it>iv. It is concluded that (i) salbutamol plasma kinetics are first-order independently of the route of administration, and (ii) salbutamol hypokaliemic effect is modulated by the dose and the route of administration.List of abbreviations
AUC
Area under salbutamol plasma concentration-time curve
- clINT
Salbutamol intrinsic clearance
- clT
Salbutamol total plasma clearance
- cMAX
Salbutamol maximal plasma concentration
-
F
Fraction of the dose of salbutamol reaching the systemic circulation
- iv
Intravenous route of administration
- it
Intratracheal route of administration
- po
Oral route of administration
- Varea
Salbutamol apparent volume of distribution
- T
2
1
Salbutamol half-life of the terminal phase
- tMAX
Time to observe the maximal decrease in plasma potassium
- eMAX
Predicted maximal effect of salbutamol
- EC50
Concentration of salbutamol eliciting 50% of eMAX
Supported by the Medical Research Council of Canada (MT-10874). Sylvie Perreault is recipient of a Bourse Formation de troisième cycle des Fonds de la Recherche en Santé du Québec. 相似文献
108.
Summary A method is described for the growth of calcium oxalate dihydrate in normal urine. Soluble chlorophyllin, at a concentration of 20 g/ml inhibited the crystallisation and the growth kinetics of the dihydrate crystals. The inhibitory capacity of chlorophyllin was compared with previous results. Data obtained suggest that the food and drug colourant chlorophyllin might be useful in the treatment of calcium oxalate stone disease. 相似文献
109.
K. Ziegler M. Frimmer W. Möller H. Fasold 《Naunyn-Schmiedeberg's archives of pharmacology》1982,319(3):254-261
Summary In vitro treatment of isolated rat hepatocytes with brominated taurodehydrocholic acid (BTC) reduced their sensitivity against phalloidin and inhibited the uptake of phalloidin as well as of cholate in an irreversible and concentration dependent manner. BTC was taken up itself by liver cells; this process was inhibited by 4,4-diisothiocyano 2,2-stilbene disulfonate (DIDS).When hepatocytes were incubated with 35S-BTC their plasma membranes contained five labeled protein species with molecular weights of 67,000, 49,000, 38,000, 32,000 and 24,000 as shown by SDS-electrophoresis. No marked difference was observed when isolated plasma membranes from livers were directly treated with the affinity label. DIDS suppressed covalent binding of 35S-BTC to membrane components drastically. Incubation of phalloidin insensitive AS-30D ascites hepatoma cells with 35S-BTC did not result in a chemical modification of the above five proteins. This agrees with an earlier observation that hepatoma cells are unable to take up phalloidin and bile acids (Petzinger et al. 1979; Rufeger and Grundmann 1977; Kroker et al. 1978).Abbreviations used BTC
brominated taurodehydrocholic acid
-
35S-BTC
35S labeled brominated taurodehydrocholic acid
- DIDS
4,4-diisothiocyano 2,2-stilbene disulfonate
- [3H]DMP
[3H]demethylphalloin
This work was supported by the Deutsche Forschungsgemeinschaft 相似文献
110.
Bone marrow biopsy instead of 'marrow juice' for cell kinetic analysis. Comparison of bone marrow biopsy and aspiration material 总被引:1,自引:0,他引:1
Wolfgang Hiddemann Thomas Büchner Michael Andreeff Bernhard Wörmann Myron R. Melamed Bayard D. Clarkson 《Leukemia research》1982,6(4):601-612
Since cell kinetic bone marrow studies have so far exclusively been carried out on aspiration material and have yielded inconsistent or even contradictory results, we investigated the adequacy and reliability of aspirates for cell kinetic analyses in comparison to biopsies. Paired samples of bone marrow (133) were taken simultaneously by aspiration and Jamshidi biopsy from 48 patients with acute leukemias and 67 patients with non-leukemic disorders. Cell kinetic analysis by (1) flow cytometry (FCM) of cellular DNA and RNA content, (2) autoradiography for [3H]TdR pulse labelling indices and (3) liquid scintillation counting of [3H]TdR uptake revealed significantly higher values in biopsies (p less than 0.001) exceeding the corresponding results from aspirates on average by factors of 1.65 for FCM S-phase index, 1.90 for G0/1 cells with high RNA content, 1.82 for [3H]TdR LI and 1.90 for [3H]TdR uptake. In more than 70% of all samples results from biopsies were 1.1-11.4 times higher, indicating that aspirates were equivalent to biopsies in fewer tan 30% of cases. Cell kinetic analysis in vitro blood/biopsy mixtures and measurements of DNA synthesis rate in corresponding aspirates and biopsies revealed that these discrepancies are due to the contamination of aspirates with non-proliferating nucleated blood cells. Biopsy, however, was found to provide representative and reproducible sampling of marrow for cell kinetic studies and should replace the presently used aspirate already characterized as "unreliable marrow juice" by Dameshek et al. in 1937 [18]. 相似文献