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101.
C. F. George T. Fenyvesi M. E. Conolly C. T. Dollery 《European journal of clinical pharmacology》1972,4(2):74-76
Summary Late plasma half-lives of dextro and racemic propranolol were measured in seven adult male subjects after 100 mg taken orally. Mean plasma half-lives of 2.38±0.43 and 2.93±0.63 h were obtained for dextro and racemic preparations respectively. In five of these subjects plasma half-lives after 50 mg dextro and laevo isomers were 2.02±0.53 and 3.20±0.42 h. No difference was found in the rates of absorption of the two isomers It is concluded that these results reflect either differences in distribution or a slower rate of metabolism of the laevo isomer. 相似文献
102.
12 schizophrenic patients were treated with large doses of propranolol, a beta-adrenergic blocking agent. 5 patients were much improved and 3 patients showed some improvements. A striking correlation was noted between the effect of propranolol and of pre-treatment urinary excretion of total cateoholamines and 3-methoxy-4-hydroxyphenylglycol (MHPG). 相似文献
103.
Rgis Levasseur Jean-Pierre Sabatier Cline Potrel-Burgot Bertrand Lecoq Christian Creveuil Christian Marcelli 《Revue du Rhumatisme》2003,70(12):1100
Sympathetic innervation has been demonstrated in bone. Adrenergic stimulation is one of the transmitters of bone loss by uncoupling between decreased bone formation and increased bone resorption.Objective. – By using a non specific antagonist of β-adrenergic pathway (propranolol per os), we hypothesized that we could rescue the uncoupling induced mechanical unloading bone loss in the rat model of tail-suspension.Materials and methods. – Twenty-two female rats Wistar, 12 week-old, have been divided into three groups: eight tail-suspended rats (SR), six tail-suspended rats treated by propranolol (SRP) and eight non suspended rats (NSR) during 30 days. Bone mineral density (BMD, g/cm2) has been measured by DXA (Hologic QDR-4500A) at D0 and D30 of the study, in the distal femoral metaphysis (DFM), the femoral diaphysis (FD), the whole body (WB, g) and body composition.Results. – Between D0 and D30, in DFM a significant variation in BMD is observed between NSR and SR (% BMD change: NSR +15.6 ± 3.1% vs. SR –1.0 ± 1.4%, P < 0.0001) and BMD rescue in SRP group (% BMD change SRP +5.3 ± 1.5% vs. SR –1.0 ± 1.4%, P = 0.03). In FD, gain of BMD is significant in NSR compared to SR (+17.5 ± 1.5% vs. +8.2 ± 2.8%, P = 0.007), and to SRP (+17.5 ± 1.5% vs + 10.1 ± 2.4%, P = 0.046). Gain in SRP group is not significant compared to SR group (P = 0.6). In WB SRP gain more BMD than NSR (+14.0 ± 1.8% vs. +5.4 ± 0.7%, P = 0.0002) and than SR (+14.0 ± 1.8% vs. +7.8 ± 1.4%, P = 0.0043). There is no difference between NSR and SR groups (P = 0.19).Conclusion. – We demonstrate that β-adrenergic pathway of sympathetic nervous system is a major transmitter pathway of mechanical loading in rat bone. A specific study is necessary to analyse a possible systemic effect of propranolol in rat bone. Propranolol could be used to prevent induced mechanical unloading bone loss as weightlessness. 相似文献
104.
Increase in plasma propranolol caused by nicardipine is dependent on the delivery rate of propranolol 总被引:1,自引:0,他引:1
A. G. Dupont I. Vercruysse D. L. Massart 《European journal of clinical pharmacology》1995,49(1-2):121-125
The influence of a single oral dose of nicardipine 30 mg on the pharmacokinetics and pharmacodynamics of propranolol 80 mg given as a conventional release formulation and as a slow release formulation was studied in two separate groups of 12 healthy volunteers. Nicardipine doubled the area under the curve (AUC) and C
max of propranolol when given as a conventional formulation, but increased it only slightly when given as a slow release formulation. This pharmacokinetic interaction did not result in clinically relevant changes in pharmacodynamic responses. These results indicate that the enhancement of the bioavailability of propranolol by coadministration of nicardipine is dependent on the delivery rate of propranolol, suggesting that the interaction is mainly due to short-term haemodynamic effects of nicardipine leading to saturation of hepatic enzymes or functional shunting. 相似文献
105.
Phasic heart rate (HR) responses and disjunctive reaction time (RT) performance were measured in 16 human subjects to investigate whether anticipatory cardiac responses differ in RT and unavoidable shock (US) tasks under propranolol and placebo conditions. Five different task conditions were randomly presented. A warning signal (S1) informed the subject about the nature of the task at the second stimulus (S2). The conditions included a control, a RT, a shock avoidance RT, an unavoidable shock, and a mixed (either a RT or US) task. Three cardiac responses occurred in the interstimulus interval: sustained acceleration (control), sustained deceleration (US), and acceleration followed by deceleration (normal-RT and avoidance-RT). The results showed that HR responses cannot be adequately interpreted without considering the type of task employed. It was concluded that both common and specific task parameters influence HR responding in RT and US tasks. 相似文献
106.
The steady state bioavailability and pharmacokinetics of propranolol over two consecutive dosing intervals were investigated in 18 black and 10 white normal volunteers following the administration of 20 mg of a test and reference oral dosage form, respectively, every 6 h. There were no differences (p greater than 0.05) between dosage forms in the mean (n = 28) area under the plasma concentration-time curve (AUC), maximum plasma concentration (Cmax) or time to Cmax (tmax) for propranolol or its active metabolite, 4-hydroxypropranolol. However, as a group blacks had lower plasma concentrations of propranolol during the second dosing interval (AUC-2 and Cmax-2, respectively) were significantly (p less than 0.05) lower in blacks, but there were no ethnic differences (p greater than 0.05) in tmax. The mean AUC and Cmax for the 4-hydroxylated metabolite during both dosing intervals were significantly (p less than 0.05) lower in blacks. Mean oral clearances of propranolol, assuming complete absorption, (range: 42.1-54.5 ml min-1 kg-1) were similar (p greater than 0.05) in each racial group. There were no substantial changes in heart rate or blood pressure in blacks or whites following propranolol administration. These data suggest that for oral propranolol, blacks have different absorption and disposition characteristics than whites. 相似文献
107.
O. Tom
íkov . Bezek M. uriov V. Faberov M. Zemnek T. Trnovec 《Biopharmaceutics & drug disposition》1984,5(2):153-162
Plasma levels and excretion of two beta-adrenoceptor blocking drugs 3H-exaprolol and 3H-propranolol wereobserved up to 96 h after a single i.v. administration to rats. Terminal half-lives of 26·8 ± 9·1 h and 51·3 ± 7·5 h were found for exaprolol and propranolol, respectively. The recovery of 3H radioactivity in feces following i.v. administration of the drus (34·2 ± 0·8 per cent and 12·0 ± 1·3 per cent 3H of exaprolol and propranolol, respectively) is of biliary origin, as 30·7 ± 3.5 per cent and 13·4 ± 3.6 per cent 3H of exaprolol and propranolol, respectively, was excreted in the bile after i.v. administration. Enterohepatic circulation of the drugs was studied using the donor-recipient rat method. After intraduodenal administration of donor bile to the recipient rat approximately 50 per cent and 40 per cent of the biliary 3H activity of exaprolol and propranolol, respectively, was re-excreted following absorption. A formula for calculating the amount of the substance together with its metabolites excreted in the bile, urine or feces as a result of enterohepatic circulation has been proposed. 相似文献
108.
The unique effect of clonidine in facilitating habituation of the acoustic startle response [10] was replicated. However, clonidine had no effect on between-session habituation, showing a pharmacological dissociation between short- and long-term habituation. Systematic manipulation of ISI showed clonidine's habituation-facilitating effect to be most striking with longer within-session ISIs where habituation was relatively weak in controls. Comparing clonidine's effect to that of two other hypotensive agents, prazosin and propranolol, showed that the habituation-facilitating effect was not due to blood pressure effects. Prazosin, an alpha1-adrenergic blocker, facilitated short-term habituation, but significantly less so than did clonidine, an alpha2-agonist. Propranolol, a beta-adrenergic blocker, had no effect of short-term habituation. Both prazosin and propranolol impaired long-term habituation, but propranolol did so without suppressing initial response levels. The data suggest that a synapse with both alpha-1- and alpha2-adrenoceptors may be critically involved in habituation of the acoustic startle response. A beta-adrenergic involvement in long-term habituation is tentatively suggested. 相似文献
109.
T. Shiga A. Fujimura T. Tateishi K. Ohashi A. Ebihara 《European journal of clinical pharmacology》1993,44(5):489-492
Summary There is diurnal variation in the absorption rate of propranolol in younger subjects. This study was undertaken to examine the effect of age on the chronopharmacokinetics of propranolol.We gave 20 mg of propranolol orally to 13 younger and 11 older hypertensive subjects at 09.00 h (day study) or 21.00 h (night study) in a cross-over design. Plasma concentrations of propranolol and its metabolites, 4-hydroxypropranolol and naphthoxylactic acid, were determined just before and at 0.5, 1, 1.5, 2, 3, 4, 6, 12, and 24 h after dosage. In the younger subjects the absorption rate constant (ka) of propranolol and its maximum plasma concentration (Cmax) were significantly higher and the time to maximum concentration (tmax) was significantly shorter in the day than at night. There were similar time-variant changes in Cmax and tmax for 4-hydroxypropranolol and naphthoxylactic acid. In contrast, there were no time-variant changes in ka, Cmax and tmax of propranolol and its metabolites in the older subjects.These results suggest that propranolol is absorbed more rapidly after morning dosing than after night-time dosing in younger but not in older subjects. Based on these findings, we speculate that the time-variance in the absorption rate or first-pass elimination, or both, of propranolol diminish with age. 相似文献
110.
The Ca++-dependent propranolol-induced increase of K+ permeability of human red blood cells, well documented in previous studies, was found to depend on extracellular K+. This was shown by studying the passive transport of 86Rb and the loss of bulk cellular K+ in both K+-free and K+-containing media. The maximal effect of propranolol was achieved with 5–10 mM K+ in incubation media. The external K+ could be substituted with TI+, but not with Na+. When added after propranolol, extracellular K+ failed to initiate the effect of propranolol on membrane permeability. The cell/medium distribution of permeant 204TI showed that the propranolol-induced increase of K+ permeability did not result in considerable hyperpolarization of the red blood cell membrane. The data obtained seem to be more consistent with a counter-transport model for explaining the propranolol effect than with a mechanism based on free diffusion of K+ through the membrane. 相似文献