共查询到20条相似文献,搜索用时 0 毫秒
1.
M. Catalano J. Parini M. Romano A. Libretti 《European journal of clinical pharmacology》1985,28(2):135-138
Summary The antihypertensive efficacy of a new long-lasting vasodilator, cadralazine, and the diuretic chlorthalidone have been compared in hypertensive patients receiving concurrent treatment with atenolol. After a 4-week run-in period with atenolol alone 100 mg/day, two groups of 10 patients whose diastolic blood pressure exceeded 100 mm Hg were given for a period of 65 days either cadralazine 15 mg/day or chlorthalidone 25 mg/day, according to a randomized, double-blind, between-patients design. Compared to atenolol alone, both cadralazine and chlorthalidone induced a statistically and clinically significant decrease in blood pressure. The antihypertensive effect did not differ significantly between groups. Good compensation of the atenolol-induced decrease in heart rate was obtained with cadralazine, whereas during atenolol + chlorthalidone treatment at times the standing heart rate was significantly lower than during treatment with atenolol + cadralazine. Side-effects, many of which were already present during atenolol treatment, occurred with a similar frequency in both groups. It is concluded that atenolol + cadralazine and atenolol + chlorthalidone are equally well tolerated, acceptable and effective in the treatment of hypertension, but that further studies are warranted to explore the potential haemodynamic advantages of the cadralazine + atenolol combination. 相似文献
2.
E. Riva P. L. Farina R. Sega G. Tognoni W. Bastain J. McAinsh 《European journal of clinical pharmacology》1980,17(5):333-337
Summary The pharmacokinetics of atenolol with and without the co-administration of chlorthalidone were studied in five hypertensive subjects. Concomitant administration of chlorthalidone appears to have little if any effect on the pharmacokinetics of atenolol during treatment for 7 days. The atenolol elimination half-lives were 6.7±1.1 and 6.3±0.9 h, respectively, with and without chlorthalidone. Two healthy volunteers also received a single 50 mg oral dose of chlorthalidone. Their blood profiles and pharmacokinetics were similar to those observed in hypertensive subjects, but a statistically significant difference (p<0.01) was found between the urinary excretion half-lives of chlorthalidone. This difference may be because chronic administration of the drug caused saturation of red cell binding. 相似文献
3.
B. Bengtsson-Hasselgren D. Elmfeldt L. Moberg O. Rönn 《European journal of clinical pharmacology》1989,37(5):459-465
Summary A study has been performed in thirteen patients with essential hypertension, WHO Class I–II, and a diastolic blood pressure 95 mm Hg, on beta-blocker (metoprolol or atenolol) monotherapy, who were also given felodipine 10 mg b.d. for 28 days. The acute and steady state blood pressure response at rest and during exercise, and the pharmacokinetics of felodipine and metoprolol, were examined.Felodipine in combination with the beta-blocker reduced the systolic and diastolic blood pressures acutely and at steady-state. The duration of the effect was longer at steady-state. There was a significant correlation between the plasma concentration of felodipine and the change in blood pressure. The increase in systolic blood pressure during exercise was of the same magnitude before and after felodipine administration. No change in resting supine heart rate was found after the administration of felodipine.There were no significant differences in the pharmacokinetics of felodipine during long-term treatment, except for the trough plasma concentration, which was increased at steady-state, even though cumulation of felodipine and its metabolite did not occur. There was a significant decrease in the maximal plasma concentration and AUC of metoprolol after 28 days of treatment with felodipine, but its elimination half-life was not changed.The adverse reactions reported during this study were those generally seen after dihydropyridines and, except for two patients who were withdrawn after the first study day, the effects were well tolerated. 相似文献
4.
S. Caponnetto E. Valvo P. Mocarelli D. Alberti S. Savonitto 《European journal of clinical pharmacology》1991,40(5):461-465
Summary A randomized multicentre between-patient study comparison has been made of the efficacy and tolerability of cadralazine and prazosin, both administered for 6 weeks to hypertensive patients with a supine diastolic blood pressure (DBP) 95 mm Hg whilst on a beta-adrenoceptor-blocker. The doses of the beta-adrenoceptor-blocker (metoprolol SR 200 mg once daily) and cadralazine (10 mg once daily) were held constant during the study, while prazosin was individually titrated from 0.5 mg to a maximum of 2 mg tds.108 patients (50 m and 58 f; mean age 54 y) were enrolled in 12 centres. Twelve patients withdrew due to adverse effects or poor efficacy (5 patients on prazosin and 7 on cadralazine).Both treatments induced a similar significant reduction in systolic blood pressure (SBP) and DBP, allowing normalization of BP in 58% of subjects on cadralazine and 55% on prazosin. Heart Rate (hR) increased significantly from 67 to 72 beats · min–1 in those on cadralazine and from 65 to 69 beats · min–1 on prazosin. Body weight was unchanged.Adverse effects were mild and typical of vasodilators, such as headache, flushing and dizziness. Physician evaluation of drug efficacy was not different between drugs, and cadralazine was rated better in terms of tolerability.Thus, in this multicentre study, cadralazine in the fixed dose of 10 mg once daily, as a second-step antihypertensive treatment in patients not satisfactorily controlled by a beta-adrenoceptor-blocker, was as effective and showed a similar side effect profile to prazosin given three times daily.For the Italian Multicentre Study Group
Participating Centres: C. Canale, V. Terrachini (Genova); G. Paoletti, A. Camerieri (Sestri Ponente); G. Gandolfi (La Spezia); A. Castelluccio, C. Mondelli (S. Remo); G. Maschio, V. Bedogna (Verona); A. Spedo (Badia Polesine); P. Cantù, A. Limido (Gallarate); F. Valentini (Como); G. Viglino (Alba); C. Martines, E. Casiglia (Piove di Sacco); R. Miori, M. Dalfollo (Trento); P. Maiolino, A. Carrozza (Cittadella) 相似文献
5.
《Current medical research and opinion》2013,29(6):378-383
SummaryIn a double-blind, crossover study in 100 elderly hypertensive patients, the hypotensive effect of a fixed combination of atenolol (50?mg) with chlorthalidone (12.5?mg) was compared with that of each of its component drugs given alone. Patients were allocated at random into two groups: one group received treatment for 4 weeks with either the combination or atenolol alone before being crossed over to the alternative medication for a further 4 weeks; the other group received either the combination or chlorthalidone alone and followed the same treatment pattern. Dosage was a single tablet per day given in the morning. Blood pressure and pulse rate were measured approximately 24 hours after dosing at the end of each treatment period. The results showed that significantly lower blood pressures were achieved, both in the standing and lying positions, with the combination than with either atenolol or chlorthalidone used alone. Combination treatment was well tolerated, few side-effects being reported and there was no significant disturbance of plasma electrolytes. 相似文献
6.
Aim: To test the effects of atenolol and amlodipine, either alone or in combination, on blood pressure, blood pressure variability (BPV), baroreflex sensitivity (BRS), and the prevalence of stroke in stroke-prone spontaneously hypertensive rats (SHR-SP). Methods: In the first set of the study, 24 8-month-old, female SHR-SP rats were randomly divided into 3 groups. Blood pressure, heart period, and BRS were determined before and after the intragastric administration of atenolol (10 mg/kg) and amlodipine (1.0 mg/kg), either alone or in combination. In the second set of the study, 40 male and 40 female rats were randomly assigned to 1 of the following 4 groups: control, atenolol (10 mg·kg^-1·d^-1), amlodipine (1.0 mg·kg^-1·d^-1), and both (10 male and 10 female in each group). The stroke incident and survival time were recorded. Results: Atenolol and amlodipine, either alone or in combination, significantly decreased blood pressure, with the exception of the amlodipine-induced effect on diastolic blood pressure. Meanwhile, only the combination treatment significantly decreased the BPV levels for the same period. The q-values calculated by the probability sum analysis were 1.17 and 2.67 for systolic and diastolic blood pressure, respectively, and were 2.48 and 2.10 for systolic and diastolic BPV, respectively, following administration. Neither drug exhibited any significant effect on BRS. Atenolol and amlodipine, either alone or in combination, significantly increased the lifespan of SHR-SP, with the best effect elicited by the combination therapy. Conclusion: A significant synergism exists between atenolol and amlodipine in lowering and stabilizing blood pressure in SHR-SP. Combination therapy may be an optimal strategy for the prevention of stroke in hypertension. 相似文献
7.
Gomides RS Costa LA Souza DR Queiroz AC Fernandes JR Ortega KC Junior DM Tinucci T Forjaz CL 《British journal of clinical pharmacology》2010,70(5):664-673
AIMS
This study was conducted to determine whether atenolol was able to decrease BP level and mitigate BP increase during dynamic resistance exercise performed at three different intensities in hypertensives.METHODS
Ten essential hypertensives (systolic/diastolic BP between 140/90 and 160/105 mmHg) were blindly studied after 6 weeks of placebo and atenolol. In each phase, volunteers executed, in a random order, three protocols of knee-extension exercises to fatigue: (i) one set at 100% of 1 RM; (ii) three sets at 80% of 1 RM; and (iii) three sets at 40% of 1 RM. Intra-arterial radial blood pressure was measured throughout the protocols.RESULTS
Atenolol decreased systolic BP maximum values achieved during the three exercise protocols (100% = 186 ± 4 vs. 215 ± 7, 80% = 224 ± 7 vs. 247 ± 9 and 40% = 223 ± 7 vs. 252 ± 16 mmHg, P < 0.05). Atenolol also mitigated an increase in systolic BP in the first set of exercises (100% =+38 ± 5 vs.+54 ± 9; 80% =+68 ± 11 vs. +84 ± 13 and 40% =+69 ± 7 vs.+84 ± 14, mmHg, P < 0.05). Atenolol decreased diastolic BP values and mitigated its increase during exercise performed at 100% of 1 RM (126 ± 6 vs. 145 ± 6 and +41 ± 6 vs.+52 ± 6, mmHg, P < 0.05), but not at the other exercise intensities.CONCLUSIONS
Atenolol was effective in both reducing systolic BP maximum values and mitigating BP increase during resistance exercise performed at different intensities in hypertensive subjects. 相似文献8.
R. van der Does L. Widmann H. -J. überbacher M. H?rrmann M. Machwirth U. Stienen 《European journal of clinical pharmacology》1990,38(Z2):S147-S152
Carvedilol [25 mg once daily] (o. d.) was compared to atenolol (50 mg o. d.) as an adjunct to pre-existing hydrochlorothiazide (HCTZ) monotherapy in patients with mild to moderate hypertension [diastolic blood pressure (DBP),100–115 mm Hg]. After a placebo run-in phase of 2 weeks, 131 patients received 25 mg HCTZ o. d. for 4 weeks. In all, 122 patients were transferred to the double-blind phase, in which 25 mg carvedilol or 50 mg atenolol was randomly added to HCTZ. After an additional 6 weeks of treatment, 112 patients were evaluable for efficacy (C/HCTZ group,n = 54; A/HCTZ group,n = 58). Blood pressure was measured and the heart rate was counted before medication, at 2-week intervals throughout the trial, and 2 h after medication on the 1st and the last day of the combination treatment period. Serum lipids were measured in addition to routine laboratory variables. A therapeutic response was defined as a reduction in supine and standing diastolic blood pressure to values of < 90=" mmhg.=" in=" a=" relatively=" low=" number=" of=" patients=" (6=" of=" 131),=" a=" response=" as=" defined=" above=" was=" achieved=" with=" hctz=" alone.=" this=" may=" be=" accounted=" for=" by=" the=" fact=" that=" patients=" were=" required=" to=" have=" a=" diastolic=" blood=" pressure=" of=" at=" least=" 100=" mghg=" and=" by=" the=" relatively=" short=" period=" of=" monotherapy.=" the=" two=" groups=" of=" patients=" receiving=" different=" combination=" treatments=" were=" well=" matched=" for=" demographic=" data=" and=" blood=" pressure=" values=" before=" the=" adjunct=" was=" added.=" in=" both=" groups=" there=" was=" a=" marked=" additional=" blood=" pressure=" decrease=" on=" the=" initiation=" of=" combined=" treatment.=" at=" the=" end=" of=" the=" study=" the=" medians=" of=" all=" blood=" pressure=" values=" were=" well=" within=" normal=" ranges,=" which=" was=" not=" the=" case=" with=" hctz=" alone.=" on=" the=" last=" day=" of=" the=" trial,=" the=" responders=" comprised=" 67%=" of=" the=" c/hctz=" group=" and=" 71%=" of=" the=" a/hctz=" group.=" no=" relevant=" changes=" in=" lipid=" values=" were=" observed=" with=" combination=" treatment=" vs=" diuretic=" monotherapy.=" no=" serious=" adverse=" event=" attributable=" to=" one=" of=" the=" study=" drugs=" was=" reported.=" the=" results=" of=" the=" present=" trial=" suggest=" that=" the=" antihypertensive=" efficacy=" of=" both=" combinations=" is=" superior=" to=" that=" of=" hctz=" alone=" and=" that=" there=" is=" no=" difference=" in=" efficacy=" between=" the=" two=" combinations.=" adding=" carvedilol=" or=" atenolol=" to=" pre-existing=" hctz=" appears=" to=" be=" safe.=" the=" tolerability=" of=" the=" antihypertensive=" treatment=" does=" not=" seem=" to=" decline,=" despite=" considerable=" additional=" decreases=" in=" blood="> 相似文献
9.
G. Muiesan E. Agabiti-Rosei A. Carotti L. Corea P. Innocenti C. Montervino R. Prezioso G. Romanelli M. Toso M. Motolese 《European journal of clinical pharmacology》1982,23(3):209-213
Summary In a multicentre, double-blind (DB), within-patient study, the antihypertensive effectiveness and tolerability of two oral administration schedules of metoprolol (M) 100 mg b.i.d. versus 200 mg once daily (o.d.), were investigated in 103 outpatients with mild to moderate essential hypertension. The study lasted 14 weeks and was divided into 3 periods: a) 2 weeks of single-blind (SB) placebo wash-out; b) 4 weeks of SB administration of M 100 mg b.i.d.; at the end of the second week of this period, chlorthalidone (C) 25 mg was added in patients with a recumbent diastolic blood pressure (BP) still >95 mmHg and was continued throughout the following period; and c) DB cross-over administration of M 200 mg/d for 4 weeks on a b.i.d. schedule and 4 weeks on a once daily schedule. In comparison with pretreatment values, heart rate and systolic and diastolic BP were reduced (p<0.001) by both M administration schedules; there was no differences between the once and twice daily treatment regimens. During M once daily, betablockade was still maintained over 24 hours or longer, as the heart rate remained significantly lower than the basal value. In 57 patients, C was added at the end of the second week of SB M administration, and a further decrease in BP was observed; again, there was no significant change during once and twice daily M administration. Unwanted effects during M treatment were of minor severity, and the majority occurred when C, too, was added. 相似文献
10.
E. van der Veur B. S. ten Berge A. J. M. Donker J. F. May F. H. Schuurman H. Wesseling 《European journal of clinical pharmacology》1984,26(2):157-162
Summary After screening a local population in the northern part of The Netherlands for hypertension, 119 patients with a diastolic pressure (DP) between 95 and 120 mmHg were randomised and treated either with 50 mg hydrochlorothiazide (n=59) or 100 mg atenolol (n=60). After 1 month of treatment 6 patients in the hydrochlorothiazide group and 24 patients in the atenolol group had reached a DP90 mmHg (p<0.001). 43 of the 50 non-responders to hydrochlorothiazide were switched to atenolol and 30 of the 35 non-responders to atenolol were changed to hydrochlorothiazide. One month after the switch 19 patients in the atenolol group and 2 patients in the hydrochlorothiazide group had reached a DP90 mmHg (p<0.001). After 6 months of treatment 32 of the 43 atenolol responders and 7 of the 8 hydrochlorothiazide responders were still receiving the same medication, as their DP was still90 mmHg. Non-responders to either medication were given the combination (n=46). 21 patients now became normotensive as did a further 10 after increasing the dose of atenolol to 200 mg. Thus, in all 70 patients had a blood pressure 90 mmHg after treatment for 4 months. Both drugs induced a significant reduction in the total of number of complaints after 1 month of treatment. They did not differ from each other. The reduction was seen both in responders and non-responders and persisted during treatment for 6 months. It is concluded that in terms of short-term efficacy the cardioselective, hydrophilic beta adrenoceptor-blocking drug atenolol is preferable to hydrochlorothiazide in the treatment of uncomplicated hypertension. 相似文献
11.
K. Laustiola A. Uusitalo T. Koivula A. Sovijärvi E. Seppälä T. Nikkari H. Vapaatalo 《European journal of clinical pharmacology》1983,25(3):293-297
Summary A study has been made of the effects of intravenous atenolol, practolol and propranolol on the changes induced by exhaustive dynamic physical exercise in blood pressure, heart rate and blood levels of lactate, glucose, insulin, free fatty acids and potassium. The mean endurance of dynamic exercise was reduced by all three beta-blockers, most markedly by propranolol. After all the beta-blockers heart rate showed a similar decrease during the first 60 min of exercise; atenolol caused the smallest reduction at exhaustion. All three beta-blockers lowered the systolic blood pressure during exercise; propranolol was the most active agent both during exercise and during recovery. The diastolic pressure was higher during exercise after treatment with the beta-blockers, especially propranolol. The beta-blockers did not markedly affect the elevation of blood glucose was abolished by atenolol. Plasma insulin was reduced by exercise after beta-blockade, most markedly after propranolol and practolol. All the beta-blockers were equipotent in reducing up to 60 min the exercise-induced increase in plasma free fatty acids, although at exhaustion propranolol had a significantly greater effect than atenolol or practolol. Serum potassium was higher after propranolol and atenolol than after practolol during exercise and recovery. 相似文献
12.
M. A. van Baak F. T. J. Verstappen B. Oosterhuis 《European journal of clinical pharmacology》1986,30(4):399-406
Summary The effects of oxprenolol, a non-selective beta-blocker with moderate intrinsic sympathomimetic activity (ISA), given by the Oros delivery system, on resting and exercise heart rate and blood pressure have been compared over a 24-h period with those of atenolol, a beta1-selective blocker without ISA. The effects on maximal and submaximal exercise tolerance and perceived exertion were studied in relation to the level of beta-blockade. 9 healthy subjects were treated with placebo, atenolol, 100 mg/day and oxprenolol Oros, 16/260 mg/day in random order, each for 5 days. Progressive maximal exercise tests and submaximal endurance tests at 80% of maximum aerobic exercise capacity were performed 2, 5 and 24 h after intake of the drugs.The reduction of blood pressure 2 and 5 h after drug intake was less pronounced after oxprenolol Oros than after atenolol, but by 24 h after the last dose the effects were similar. The peak level of beta-blockade (i.e. reduction in maximal exercise heart rate) was similar after oxprenolol Oros and atenolol. The minimal level of beta-blockade 24 h after the last dose was greater after oxprenolol Oros than after atenolol. Maximal exercise capacity and submaximal exercise tolerance were impaired after both beta-blockers. The subjective feeling of exertion did not differ between placebo, atenolol and oxprenolol Oros when related to the relative work load, except after the first minute of exercise, when the rating of perceived exertion was higher after atenolol. 相似文献
13.
A. Lechi S. Pomari R. Berto P. Buniotto A. Parrinello F. Marini L. Cogo A. Tomasi G. Baretta 《European journal of clinical pharmacology》1982,22(4):289-293
Summary In a multicentre, double-blind, crossover, placebo-controlled study, the antihypertensive effect of labetalol 100 mg and chlorthalidone 10 mg, given alone or in combination, has been assessed in 32 hypertensive patients. The combination had a greater effect in reducing blood pressure than did its separate components. This was particularly evident after exercise. Heart rate increased during chlorthalidone therapy, decreased during labetalol therapy, and a summation effect was observed during treatment with the combination. In most cases additivity was observed, as no interaction between the single components was observed, except for heart rate after exercise, and for diastolic blood pressure in the upright position. No interaction was observed either in the biochemical indices or in the clinical side-effects. 相似文献
14.
L. A. Ferrara G. de Simone M. Mancini M. L. Fasano F. Pasanisi G. Vallone 《European journal of clinical pharmacology》1984,27(5):525-528
Summary The presence of a possible correlation between changes in left ventricular mass of hypertensive patients and the degree of blood pressure reduction with different antihypertensive drugs has been investigated in 40 outpatients by M-mode echocardiography. Ten of these, with blood pressure in normal limits with different antihypertensive treatment had their therapy changed in chlorthalidone 25 mg/day without any run-in (Group A); other 30 patients, with a previously uncontrolled blood pressure, after a 14 day run-in, were randomly allocated to chlorthalidone 25 mg/day (Group B), slow release nifedipine 20 mg/day (Group C) or placebo (Group D). At the end of the eight week treatment period a further decrease in systolic blood pressure was observed in Group A without changes in ventricular mass; an highly significant decrease in both systolic and diastolic blood pressure was observed in B and C but only patients on chlorthalidone changed their ventricular mass; no change in both blood pressure and ventricular mass was observed on placebo. As changes in ventricular mass are not correlated with blood pressure reduction, we conclude that other, not well defined factors, apart from the decrease in duration and degree of left ventricular systolic wall tension, may be responsable for reversal of left ventricular hypertrophy. 相似文献
15.
目的 通过对比肾血管性高血压(RVH)与原发性高血压(EH)患者24h动态血压,以研究两者之间的差异.方法 应用动态血压监测仪测定30例RVH患者的24 h动态血压,同时选择30例年龄、性别与之相匹配的EH患者行24h动态血压测定,比较两者之间的差异.结果 RVH组患者24 h、白昼、夜间的收缩压、舒张压及脉压测定的平均值,均高于EH组(P <0.01);RVH组患者的24 h收缩压负荷、舒张压负荷分别为58.33%和38.41%,而EH组患者则为29.01%和22.38%,两组比较差异有统计学意义(P<0.05)).EH组有63.30%的患者夜间血压下降率>10%,血压曲线以杓型为主;而RVH组只有26.70%的患者夜间血压下降率≥10%,血压曲线以非杓型为主.结论 RVH患者动态血压均值和血压负荷增加明显,昼夜节律减弱. 相似文献
16.
R. Vandongen B. Margetts L. J. Beilin N. deKlerk P. Rogers 《European journal of clinical pharmacology》1986,30(3):283-287
Summary This study examines and compares the hemodynamic and sympathoadrenal response to bicycle exercise in hypertensive subjects during two weeks' treatment with a cardio-selective (metoprolol) and nonselective (propranolol) beta-blocker. The increase in plasma norepinephrine and epinephrine concentration following exercise was augmented to a similar degree with each beta-blocker. Pre-exercise blood pressure and heart rate were similar for the two drugs. However immediately after exercise and particularly after resting for 20 min post exercise, diastolic blood pressure was lower during metoprolol treatment. Systolic blood pressure was also lower 20 min post exercise during metoprolol treatment. These observations indicate that cardio-selective beta-blockers offer advantages in blood pressure control during exercise through intact vascular 2-adrenoceptors opposing sympathetically mediated vasoconstriction. 相似文献
17.
Summary Eleven patients were treated for essential hypertension with metoprolol (Selokén®) for more than three months. The time course of changes in blood pressure, pulse rate and plasma renin activity was studied during treatment with an oral maintenance dose of 100 mg twice daily. Significant decreases in pulse rate, diastolic blood pressure and plasma renin activity were observed even after the first dose. The plasma concentration of metoprolol reached equilibrium after the second dose. After the third dose there was no further significant change in blood pressure. There was a significant correlation (p<0.001) between the initial (after three doses) and final (after >90days) effect of metoprolol on blood pressure (r=0.86 and 0.91 for systolic and diastolic blood pressure change, respectively). 相似文献
18.
Doxazosin in combination with atenolol in essential hypertension: a double-blind placebo-controlled multicentre trial 总被引:1,自引:0,他引:1
M. Searle R. Dathan S. Dean C. C. Christensen A. Westheim 《European journal of clinical pharmacology》1990,39(3):299-300
Doxazosin (mean dose 11 mg) given once daily in combination with 100 mg atenolol (n = 44) was compared with placebo and atenolol (n = 43) in a double-blind, multicenter study in patients with mild to moderate essential hypertension. In the atenolol/doxazosin-treated group, standing blood pressure significantly decreased by 17.0/12.3 mm Hg compared to 6.2/6.7 mm Hg in the atenolol/placebo group whereas supine blood pressure decreased by 13.2/9.8 mm Hg and 9.2/6.0 mm Hg, respectively in the two groups. Serum lipids did not change significantly in either group. The majority of side-effects reported were mild and transient. This study confirms that doxazosin may be safely combined with a beta-blocker. Doxazosin proved to be well tolerated and effective in patients with blood pressure refractory to atenolol alone. 相似文献
19.
G. Leonetti L. Terzoli C. Bianchini C. Sala A. Zanchetti 《European journal of clinical pharmacology》1980,18(5):365-374
Summary To show whether repeated administration of atenolol for several days would influence its pharmacokinetic parameters and the extent and duration of the pharmacologic responses, the plasma level of atenolol and changes in heart rate, blood pressure and plasma renin activity were measured in 12 hypertensive patients at various times of day (9 a. m., 12 noon, 3 p. m. and 7 p. m.) after oral administration of the first dose of atenolol 100 mg, again during the 7th and 14th days of continued once-daily administration of the same dose, and finally during the three days following withdrawal of the drug. The peak plasma concentration of atenolol (about 600 ng/ml) was found 3 h after administration of the first dose, and measurable amounts (50–70 ng/ml) were found after 24 h. None of the pharmacokinetic characteristics were changed by administration of a single daily dose for two weeks. After withdrawal of the drug, detectable amounts of atenolol were found in plasma for at least 48 h. The first dose of atenolol caused prompt (3 h) and prolonged (up to 24 h) lowering of supine and standing systolic and diastolic blood pressures, slowing of supine and standing heart rate, reduction of the blood pressure and heart rate responses to dynamic exercise, and a decrease in plasma renin activity. The extent and time-course of all these responses were not influenced by repeated once-daily administration of the 100 mg dose for two weeks. Most of the effects continued during the withdrawal days, the lowering of blood pressure being somewhat more prolonged than the slowing of heart rate. It is concluded that a once-daily dose of atenolol 100 mg decreases blood pressure and heart rate throughout the following 24 h, without excessive daily fluctuation in its effects, and without signs of tolerance or accumulation. 相似文献
20.