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81.
M. Depré D. J. Margolskee A. Van Hecken J. S. Y. Hsieh A. Buntinx P. J. De Schepper J. D. Rogers 《European journal of clinical pharmacology》1992,43(4):431-433
Summary The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i. v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i. v. doses of MK-571 at weekly intervals.The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, ll-, and 2.3 fold. Regardless of dose, the elimination of L-668,018 was more rapid than that of MK-0679.The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition. 相似文献
82.
G. Sutherland M. A. H. Russell J. Stapleton C. Feyerabend O. Ferno 《Psychopharmacology》1992,108(4):512-518
Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed. 相似文献
83.
二甲苯胺基噻唑与金莲橙OO在pH2.0生成复合物可用氯仿抽提,分离的复合物在盐酸中用锌还原.还原金莲橙有强的燐光,激发波峰302nm,发射波峰442nm,燐光强度与二甲苯胺基噻唑量成正比.用此法研究其在小鼠体内的吸收、分布、排泄及作药物动力学研究.小鼠im二甲苯胺基噻唑10mg/kg后5min,在血、脑、膈、肺、心、肝、脾、肾、尿及胆中都有药物存在.高峰在给药后30min,6h后各组织中还有不少量药物存在,24h内二甲苯胺基噻唑在小鼠尿中排泄25μg,粪便中排泄1.63μg,共计排泄26.6μg,占给药量的9.67%.兔、大鼠、小鼠im二甲苯胺基噻唑10mg/kg后不同时间测血药浓度,作药物动力学分析,其为二室开放模型药物.三种动物的主要动力学参数为:t_(1/2) 126.2,165.4,207.5min;高峰时间35.1,23.5,17.1min;AUC为416.1,298.3,385.2μg-min/ml;廓清率为24,33.7,26ml/min保定宁吸收速率比它快一倍,半吸收期为2.45min,高峰时间为11.7min. 相似文献
84.
85.
G. Vinçon C. Baldit P. Couzigou F. Demotes-Mainard L. Elouaer-Blanca Dr. B. Bannwarth B. Begaud 《European journal of clinical pharmacology》1992,43(5):559-562
Summary The pharmacokinetics of famotidine has been investigated in ascitic cirrhotic patients. 10 decompensated cirrhotic patients were studied (9 m, 1 f), who had normal renal function, and six healthy control subjects (4 m, 2 f), matched for age, sex and weight. Each subject received on two occasions, at least four days apart, a single oral (40 mg) or intravenous dose (20 mg) of famotidine, at 21.00 h in a randomised manner. Serial blood samples were collected and famotidine in plasma was determined by a HPLC/UV method. Plasma data were subjected to non compartmental pharmacokinetic analysis.There were no statistically significant differences in pharmacokinetic parameters between the two groups after either the intravenous or oral administration of famotidine.The findings suggest that the dose of famotidine may not require any adjustment in ascitic patients without renal failure. 相似文献
86.
Summary The pharmacokinetics of isradipine, a calcium-channel blocker, have been studied in eight patients on chronic haemodialysis. A single oral dose of 5 mg was administered on both a non-haemodialysis and a haemodialysis day and the plasma concentrations of isradipine were analyzed.The mean cmax, tmax, AUC, and t1/2 in plasma on the non-haemodialysis day were 5.2 ng·ml–1, 1.4 h, 23.8 ng·h·ml–1, and 3.1 h, respectively. The dialysis clearance of isradipine was negligible (5.0 ml·min–1).The t1/2 values during haemodialysis were not significantly different from those observed during the same period post dose on the non-haemodialysis day. The study demonstrates that supplemental doses of isradipine are not necessary in these patients since isradipine is not significantly removed by haemodialysis. 相似文献
87.
P. H. Mogensen L. Jórgensen J. Boas M. Dam A. Vesterager G. Flesch P. K. Jensen 《Acta neurologica Scandinavica》1992,85(1):14-17
The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required. 相似文献
88.
Luis H. Ramirez Morbize Juliéron Marc Bonnay Serge Koscielny Zhongxin Zhao Alain Gouyette Jean-Nicolas Munck 《Investigational new drugs》1995,13(1):51-53
Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed
that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs.
Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits,
and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment
course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis
andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory
effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further
trials in patients with squamous cell carcinomas. 相似文献
89.
Donald B. White Cynthia A. Walawander Dong Y. Liu Thaddeus H. Grasela 《Journal of pharmacokinetics and pharmacodynamics》1992,20(3):295-313
In a simulation study of inference on population pharmacokinetic parameters, two methods of performing tests of hypotheses comparing two populations using NONMEM were evaluated. These two methods are the test based upon 95% confidence intervals and the likelihood ratio test. Data were simulated according to a monoexponential model and, in that context, power curves for each test were generated for (i)the ratio of mean clearance and (ii)the ratio of the population standard deviations of clearance. To generate the power curves, a range of these parameters was employed; other pharmacokinetic parameters were selected to reflect the variability typically present in a Phase II clinical trial. For tests comparing the means, the confidence interval tests had approximately the same power as the likelihood ratio tests and were consistently more faithful to the nominal level of significance. For comparison of the standard deviations, and when the volume of information available was relatively small, however, the likelihood ratio test was more able to detect differences between the two groups. These results were then compared to results on parameter estimation in order to gain insight into the question of power. As an example, the nonnormality of estimates of the ratio of standard deviations plays an important role in explaining the low power for the confidence interval tests. We conclude that, except for the situation of modeling standard deviations with only sparse information, NONMEM produces tests of significance that are effective at detecting clinically significant differences between two populations.Partial support from the Upjohn Company, NIH-BRSG SO RR 07066, and the Burroughs Wellcome Foundation. 相似文献
90.
阿昔洛韦片剂和胶囊在人体的生物利用度 总被引:2,自引:0,他引:2
10名男性受试者按交叉实验设计口服阿昔洛韦片剂和胶囊各400 mg 后,用改良的 HPLC 测定血药浓度,计算表明阿昔洛韦胶囊口服后吸收快于片剂,峰浓度也较高,但吸收程度(AUC_(0-12h))相似。 相似文献