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排序方式: 共有98条查询结果,搜索用时 15 毫秒
1.
F. M. Belpaire M. G. Bogaert M. Rosseneu 《European journal of clinical pharmacology》1982,22(3):253-256
Summary The binding of 8 -adrenergic blocking drugs to human serum albumin, to 1-acid glycoprotein and to serum from normal volunteers and from patients with rheumatoid arthritis was studied. Protein binding was determined in vitro using equilibrium dialysis of labelled drug at 25° C. Oxprenolol and propranolol were highly bound to serum, alprenolol, pindolol and timolol to a lesser degree, and atenolol, metoprolol and sotalol were negligibly bound. For the five compounds which were appreciably bound, the mean binding was significantly higher in serum from patients with rheumatoid arthritis than in serum from normal volunteers. For those drugs, binding to 1-acid glycoprotein was higher than to human serum albumin, and binding to a mixture of both proteins approached that to serum from healthy volunteers. For each of these drugs there was a strong correlation between the serum 1-glycoprotein concentration and the percentage binding. 相似文献
2.
O. Teirlynck F. M. Belpaire F. Andreasen 《European journal of clinical pharmacology》1982,21(5):427-431
Summary A comparison was made between the binding of the anti-arrhythmic agents aprindine and moxaprindine to human serum, to human serum albumin (HSA), to 1-acid glycoprotein (1-AGP) and to a mixture of HSA and 1-AGP. In serum from healthy volunteers (n=4) the binding of aprindine-HCl 5 µg/ml (13.8 µM) was 93.8% (SD±1.0), and that of moxaprindine-HCl 5 µg/ml (12.8 µM) was 94.1% (SD±1.1). Their binding to the mixture of 1-AGP and albumin approximated their binding to serum. For 1-AGP, the binding was similar for both compounds, whereas for HSA the binding of aprindine was more pronounced than that of moxaprindine: for both products the affinity coefficient for binding to 1-AGP was about 100 times greater than that for binding to albumin. In serum from rheumatoid patients and from patients with renal failure a small but significant increase in binding of aprindine and moxaprindine was observed, approximately 1%. Increased and decreased binding was seen in serum from cirrhotic patients; for example, for aprindine the range in cirrhosis was 96.7%–79.8%, and the range in controls was 95.0%–92.4%. Free drug fraction and 1-AGP concentration were inversely correlated. The results show that 1-AGP plays an important role in the binding of aprindine and moxaprindine, and that alteration in the binding of the two compounds in disease states to a large extent can be explained by changes in serum 1-AGP concentration. 相似文献
3.
4.
M. M. Mussche F. M. Belpaire M. G. Bogaert 《European journal of clinical pharmacology》1975,9(1):69-71
Summary Plasma protein binding capacity for phenylbutazone has been studied in 4 patients with acute renal failure. There was an initial important decrease in binding capacity, which gradually returned to normal with improvement of renal function. 相似文献
5.
A F De Rick F M Belpaire C Dello M G Bogaert 《The Journal of pharmacology and experimental therapeutics》1987,241(1):289-293
The pharmacokinetics and the antiarrhythmic effect of lidocaine were studied in healthy dogs on three occasions: before administration of rifampicin, on the 14th day of treatment with rifampicin and 4 weeks after stopping rifampicin treatment. On each occasion a loading and a maintenance infusion of lidocaine were given to obtain steady-state concentrations. Blood and plasma concentrations of lidocaine, alpha-1-acid glycoprotein plasma concentrations and percentage of free lidocaine in plasma were determined at the end of the maintenance infusion. The antiarrhythmic effect of lidocaine was evaluated by measuring the arrhythmogenic dose of epinephrine. Blood concentrations and, consequently, the total blood clearance of lidocaine were comparable on the three occasions. Total plasma concentrations were significantly higher after rifampicin administration as compared to the two control periods. Percentage of free lidocaine decreased from about 50 to about 30%, accompanied by a nearly 3-fold increase of alpha-1-acid glycoprotein concentrations. Free plasma concentrations were slightly lower after rifampicin treatment. The epinephrine dose ratio (before/after) paralleled the changes in free lidocaine concentrations. The correlation between free plasma concentrations and epinephrine dose ratio was much stronger than between total plasma concentrations and epinephrine dose ratio. The plasma elimination half-life of lidocaine was markedly shortened after rifampicin treatment, due to a diminished volume of distribution. It is concluded that, under steady-state conditions, marked increases in the protein binding of lidocaine are accompanied by only slight decreases of free plasma concentrations and of antiarrhythmic effect. 相似文献
6.
In-vitro biotransformation of antipyrine, lignocaine and propranolol in the liver of rats with turpentine-induced inflammation 总被引:1,自引:0,他引:1
B Chindavijak F M Belpaire M G Bogaert 《The Journal of pharmacy and pharmacology》1987,39(11):883-886
In rats with inflammation induced by turpentine injection, changes in drug disposition occur in-vivo and in the perfused isolated liver. Therefore the biotransformation of a low extraction drug, antipyrine, and of two high extraction drugs, lignocaine and propranolol, has been evaluated in the 9000g supernatant fraction of the liver of turpentine-treated rats. Aminopyrine N-demethylase activity and cytochrome P450 content were also measured. Turpentine treatment significantly reduced the in-vitro breakdown of the three drugs; aminopyrine N-demethylase activity and cytochrome P450 content were also decreased. Similar results were found in the proadifen-treated rats, except that in those, the cytochrome P450 content was slightly increased. The changes in drug disposition seen after turpentine-induced inflammation, could therefore be due in part to a change in hepatic enzymatic activity. 相似文献
7.
Apolipoprotein E quantified by enzyme-linked immunosorbent assay 总被引:4,自引:0,他引:4
We developed a sensitive, specific "sandwich"-type enzyme-linked immunosorbent assay in which affinity-purified antibodies are used for coating and also for preparing an antibody-peroxidase conjugate to quantify apolipoprotein E in serum and in its lipoprotein fractions. This technique is rapid (results within 5 h), precise (mean intra- and interassay CVs 4.3 and 8.2%, respectively), accurate, and simple to perform. Sample pretreatment did not enhance apo E immunoreactivity. For 47 normolipidemic subjects, the mean apo E concentration was 38.11 (SD 11.1) mg/L. Above-normal apo E concentrations were measured in all types of hyperlipoproteinemia, especially types III and V. Apo E correlated with triglyceride (r = 0.58) and cholesterol concentrations (r = 0.60). As determined by gel filtration, hypertriglyceridemia was associated with a redistribution of apo E towards the triglyceride-rich lipoprotein fractions, which contained 77.1% (SD 16.8%) of total plasma apo E in Fredrickson type V patients, compared with 12.5% (SD 6.3%) in normal persons. 相似文献
8.
Van Sassenbroeck DK De Neve N De Paepe P Belpaire FM Verstraete AG Calle PA Buylaert WA 《Clinical toxicology (Philadelphia, Pa.)》2007,45(5):533-538
Case reports mention a sudden awakening from GHB-associated coma but do not specify its time course. The aim of the present case series was to investigate the time course of the awakening from GHB intoxication and the relationship to plasma concentrations of GHB and the presence of other drugs. Unconscious (GCS or=12 was 30 minutes (range 10 to 50 minutes). A subgroup of five patients had a GCS of 3 upon arrival and remained at 3 for a median time of 60 minutes (range 30 to 110 minutes), while the median time for the transition between the last point with GCS 3 and the first with GCS 15 was 30 minutes (range 20 to 60 minutes). This case series illustrates that patients with GHB intoxications remain in a deep coma for a relatively long period of time, after which they awaken over about 30 minutes. This awakening is accompanied by a small change in GHB concentrations. A confounding factor in these observations is co-ingested illicit drugs. 相似文献
9.
M De Paepe F Belpaire K Schelstraete N Lameire 《The Journal of laboratory and clinical medicine》1988,111(4):421-429
Four peritoneal volume markers (carbon 14-labeled dextran, dextran blue, radioactive albumin, and hemoglobin) were compared. In six rabbits 14C-dextran was compared with dextran blue during a 4-hour "dwell" with a 4.25% dextrose solution. The recovery of 14C-dextran at the end of the dwell was 71% +/- 3% vs. 92% +/- 1% for dextran blue (P less than 0.001). In six other rabbits, radioactive albumin (RISA) was compared with dextran blue. The recovery of RISA was 78% +/- 4%, compared with 85% +/- 2% for dextran blue (P less than 0.05). The calculated peritoneal volumes, uncorrected for disappearance of the markers, were consistently higher than when correction was made. After correction, the calculated end volumes were similar to actually measured end volumes. In six patients with chronic ambulatory peritoneal dialysis, the intraperitoneal volume during a single dwell of 6 hours was estimated in paired observations with lactated Ringer's solution and 1.5% dextrose dialysate, using simultaneously autologous hemoglobin and RISA. In eight additional patients, a single dwell with 4.25% dextrose dialysate was studied. The recoveries of both markers were related to the osmotic strength of the dialysate. Recoveries were 66.7% +/- 2.3% and 69.6% +/- 0.9% in lactated Ringer's solution, and increased to 81% +/- 3% and 82% +/- 2% in 4.25% dextrose for hemoglobin and RISA, respectively. With each dialysate, after correction for disappearance of the marker, no differences in volume profiles or between calculated or measured end volumes could be found with either hemoglobin or RISA.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
10.
Paroxetine affects metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers 总被引:5,自引:0,他引:5
Hemeryck A Lefebvre RA De Vriendt C Belpaire FM 《Clinical pharmacology and therapeutics》2000,67(3):283-291
OBJECTIVE: To investigate the effect of multiple-dose paroxetine intake on the stereoselective pharmacokinetics and the pharmacodynamics of metoprolol. METHODS: We conducted an open trial with two sessions in eight healthy male volunteers. Racemic metoprolol (100 mg single oral dose) was administered before and after paroxetine treatment (20 mg/day for 6 days). The (R)- and (S)-metoprolol pharmacokinetics, metoprolol metabolic ratio (MR), exercise heart rate and blood pressure were assessed for 12 (pharmacodynamic data) to 24 (pharmacokinetic data) hours after each metoprolol intake. RESULTS: Paroxetine treatment increased the mean area under the plasma concentration-time curve extrapolated to infinity (AUC) of (R)- and (S)-metoprolol significantly (169 to 1,340 ng x h/mL [P < .001] and 279 to 1,418 ng x h/mL [P < .001], respectively), with an approximately twofold increase in both maximum plasma concentration and terminal elimination half-life. Furthermore, the (S)/(R) AUC ratio was significantly decreased, from 1.72 to 1.07 (P < .001). The mean metoprolol MR was significantly increased, from 0.17 to 5.69 (P < .05). The AUC of the metoprolol-induced decrease in exercise heart rate versus time curve was increased, with 46% (P < .01) after multiple-dose paroxetine intake, reaching significance from 6 hours after metoprolol intake, illustrating a more sustained beta-blockade. Similar results were obtained for the effect on exercise systolic blood pressure. Multiple-dose metoprolol administration combined with paroxetine can lead to an accumulation of the beta-blocking (S)-enantiomer of metoprolol, possibly resulting in unacceptable bradycardia, loss of cardioselectivity, or both. CONCLUSION: Multiple-dose paroxetine intake affects both metoprolol pharmacokinetics and pharmacodynamics and suggests that when paroxetine is added to an ongoing metoprolol therapy, caution is warranted and a reduction of the metoprolol dose may be required to prevent undesired adverse effects. 相似文献