共查询到20条相似文献,搜索用时 140 毫秒
1.
Objective: To compare the effects on the hypothalamo-pituitary-adrenal (HPA) axis of budesonide, delivered via Turbuhaler at doses
of 800 μg once daily in the morning or evening or 400 μg twice daily.
Methods: Healthy men (n=24) received four treatments in random order: budesonide, 800 μg in the morning and placebo in the evening; budesonide, 800 μg
in the evening and placebo in the morning; budesonide, 400 μg in the morning and evening; placebo in the morning and evening.
Each treatment was given for 1 week, with a 2-week washout period between treatments. Blood samples for measurement of plasma
cortisol were obtained before the evening dose on day 6 of each treatment period and over the following 22 h.
Results: All three budesonide regimens produced a statistically significant reduction (mean 16–19%) in the area under the curve of
plasma cortisol concentration versus time over 22 h (AUC0–22h) compared with placebo. There were no statistically significant differences among the three regimens. These reductions in
plasma cortisol concentrations were not considered to be clinically significant. Analysis of the fractional AUCs measured
0–10 h and 10–22 h after dosing showed that evening dosing had a greater effect on nocturnal cortisol than morning dosing;
daytime cortisol was reduced by all treatments.
Conclusion: There was no significant difference between the effects on plasma cortisol of budesonide 400 μg twice daily and 800 μg once
daily in the morning or evening.
Received: 1 January 2000 / Accepted: 15 March 2000 相似文献
2.
Rationale There has been controversy over the abuse potential of methylphenidate (MPH) in the context of treatment for attention deficit
hyperactivity disorder (ADHD).
Objective The objective of this study was to compare the reinforcing and subjective effects of oral MPH in adults with and without ADHD.
Materials and methods Following screening, 33 adults (n = 16 with ADHD; n = 17 free from psychiatric diagnoses) completed four pairs of experimental sessions, each of which included a sampling session
and a self-administration session. During sampling sessions, subjects received in randomized order 0 (placebo), 20, 40, and
60 mg MPH. During self-administration sessions, subjects completed a progressive ratio (PR) task to earn portions of the dose
received on the corresponding sampling session. Subjective effects were recorded throughout all sessions. The main outcome
measure for the study was the number of ratios completed on the PR task. Secondary measures included peak subjective effects
and area-under-the-curve values for subjective effects.
Results Compared to the control group, the ADHD group completed more ratios on the PR task. Both groups showed robust effects of methylphenidate
on subjective endpoints. Main effects of group were noted on subjective effects involving concentration and arousal.
Conclusions Compared to placebo, MPH produced reinforcing effects only for the ADHD group and not for the control group. Increases in
stimulant-related subjective effects in non-ADHD subjects were not associated with drug reinforcement.
相似文献
Scott H. KollinsEmail: |
3.
The effect of itraconazole on the pharmacokinetics and pharmacodynamics of oral prednisolone 总被引:2,自引:0,他引:2
Objective: To examine the possible effect of itraconazole on the pharmacokinetics and pharmacodynamics of orally administered prednisolone.
Methods: In this double-blind, randomised, two-phase cross-over study, ten healthy subjects received either 200 mg itraconazole or
placebo orally once a day for 4 days. On day 4, 20 mg prednisolone was given orally. Plasma concentrations of prednisolone,
cortisol, itraconazole, and hydroxyitraconazole were determined by means of high-performance liquid chromatography up to 47 h.
Results: Itraconazole increased the total area under the plasma prednisolone concentration–time curve by 24% (P < 0.001) and the elimination half-life of prednisolone by 29% (P < 0.001) compared with placebo. The peak plasma concentration and time to the peak of prednisolone were not affected by itraconazole.
The mean morning plasma cortisol concentration, measured 23 h after the ingestion of prednisolone, during the itraconazole
phase was 73% of that during the placebo phase (P < 0.001).
Conclusions: The observed minor interaction between itraconazole and oral prednisolone is probably of limited clinical significance.
The susceptibility of prednisolone to interact with CYP3A4 inhibitors is considerably smaller than that of methylprednisolone,
and itraconazole and probably also other inhibitors of CYP3A4 can be used concomitantly with prednisolone without marked changes
in the effects of this corticosteroid.
Received: 4 October 1999 / Accepted in revised form: 29 November 1999 相似文献
4.
Rationale There are complex relationships between stress and smoking; smoking may reduce the emotional discomfort of stress, yet nicotine
activates stress systems and may alter responses to acute stress. It is important to understand how smoking affects physiological
and psychological outcomes after stress and how these may interact to motivate smoking.
Objectives This study aimed to examine the magnitude and time course of hormonal, cardiovascular, and psychological responses to acute
psychosocial stress in smokers and non-smokers to investigate whether responses to acute stress are altered in smokers.
Materials and methods Healthy male non-smokers (n = 20) and smokers (n = 15) participated in two experimental sessions involving a standardized public speaking stress procedure and a control non-stressful
task. The outcome measures included self-reported mood, cardiovascular measures (heart rate and blood pressure), and plasma
hormone levels (noradrenaline, cortisol, progesterone, and allopregnanolone).
Results Smokers exhibited blunted increases in cortisol after the Trier Social Stress Test, and they reported greater and more prolonged
subjective agitation than non-smokers. Stress-induced changes in progesterone were similar between smokers and non-smokers,
although responses overall were smaller among smokers. Stress did not significantly alter levels of allopregnanolone, but
smokers exhibited lower plasma concentrations of this neurosteroid.
Conclusions These findings suggest that smoking dampens hormonal responses to stress and prolongs subjective discomfort. Dysregulated
stress responses may represent a breakdown in the body’s ability to cope efficiently and effectively with stress and may contribute
to smokers’ susceptibility to acute stress, especially during abstinence. 相似文献
5.
Simon NM Connor KM LeBeau RT Hoge EA Worthington JJ Zhang W Davidson JR Pollack MH 《Psychopharmacology》2008,197(4):675-681
Rationale More data are needed to guide “next step” strategies for patients with generalized anxiety disorder (GAD) remaining symptomatic
despite initial pharmacotherapy.
Objective This study prospectively examined the relative efficacy of quetiapine versus placebo augmentation for individuals with GAD
remaining symptomatic with initial paroxetine CR pharmacotherapy.
Materials and methods Adult outpatients with GAD were recruited from 2004 to 2007 at two academic centers. Phase 1 consisted of 10 weeks of open-label
paroxetine CR flexibly dosed to a maximum of 62.5 mg/day. Those remaining symptomatic (Hamilton Anxiety Scale [HAM-A] ≥ 7)
at week 10 were randomized to quetiapine or placebo augmentation flexibly dosed from 25 to 400 mg/day.
Results For participants receiving paroxetine CR (n = 50), there was a significant reduction in HAM-A scores (baseline mean ± SD = 22.4 ± 4.2 to endpoint mean ± SD = 11.2 ± 6.9;
paired t = 12.1, df = 49, t < 0.0001) with 40% (n = 20) achieving remission. Counter to our hypothesis, we did not find significant benefit for quetiapine augmentation of
continued paroxetine CR (HAM-A reduction mean ± SD = 2.6 ± 5.8 points quetiapine, 0.3 ± 5.5 points placebo; t = 0.98, df = 20, p = n.s.) in the randomized sample (n = 22) with relatively minimal additional improvement overall in phase 2.
Conclusions Although conclusions are considered preliminary based on the relatively small sample size, our data do not support the addition
of quetiapine to continued paroxetine CR for individuals with GAD who remain symptomatic after 10 weeks of prospective antidepressant
pharmacotherapy and suggest that further research examining strategies for GAD refractory to antidepressants is needed. 相似文献
6.
D. Taverner L. Bickford S. Shakib A. Tonkin 《European journal of clinical pharmacology》1999,55(7):509-513
Objectives: To evaluate the dose-response relationship of increasing doses of oxymetazoline compared with placebo in normal subjects,
and to determine the sensitivities of rhinomanometry, acoustic rhinometry and symptoms in discriminating between differing
doses of oxymetazoline in normal subjects.
Methods: The study had a randomized, double-blind, placebo-controlled, parallel group, dose-response design. One hundred and twenty-five
healthy volunteers with no nasal obstruction were randomized to administration of a single intra-nasal dose of oxymetazoline
(6.25 μg, 12.5 μg, 25 μg or 50 μg) or placebo to each nasal cavity. Nasal airway resistance (NAR) was measured by active posterior
rhinomanometry. Total minimum cross-sectional area (tMCA) and volume (tVOL) were measured by acoustic rhinometry. Symptoms
of congestion (CON) were assessed on a visual analogue scale.
Results: The two highest doses of oxymetazoline produced a significant decrease in NAR compared with placebo (P = 0.015) but not between placebo and 12.5 μg or 6.25 μg. There was a dose-response relationship for tVOL, which increased
significantly after all doses compared with placebo (P < 0.001) and showed differences between 6.25-μg and 25-μg (P < 0.014) and 12.5-μg and 50-μg (P < 0.05) doses. tMCA increased compared with placebo after all treatments (P = 0.028), but there were no significant differences between any of the active doses. There were no significant changes in
CON after any treatments compared with placebo.
Conclusions: tVOL shows a clear dose-response relationship for the range of doses of oxymetazoline administered. tVOL provides a sensitive
and discriminatory measure of small nasal changes after low doses of oxymetazoline. NAR is able to discriminate between doses,
but is less sensitive than tVOL and tMCA, requiring a higher threshold dose before significant changes are seen in nasal patency.
Received: 1 March 1999 / Accepted in revised form: 17 May 1999 相似文献
7.
A. M. Wilson D. J. Clark L. McFarlane B. J. Lipworth 《European journal of clinical pharmacology》1997,53(1):33-37
Study objective: This study was conducted to compare the adrenal suppression of inhaled fluticasone propionate and triamcinolone acetonide
in healthy volunteers, both given via their respective pressurised metered dose inhaler (pMDI) devices at high doses within
the manufacturers recommended dose range.
Design: We used a single (investigator) blind, randomised, crossover design comparing a total daily dose of 1.625 mg fluticasone
propionate delivered via a pMDI, 1.60 mg daily of triamcinolone acetonide delivered via a pMDI with integrated spacer, or
placebo pMDI; each drug was given in two divided doses at 0800 hours and 2200 hours over a 24-h period. Each drug treatment
was separated by a 1-week washout.
Patients: Twelve normal subjects mean age 27.5 years were studied.
Measurements: Blood samples were taken for 0800 hours plasma cortisol, i.e. 10 h following the second dose. Ten hour urine collections
(2200 hours until 0800 hours) were taken for urinary cortisol and creatinine excretion.
Results: For the 0800 hours plasma cortisol (geometric mean, nmol · l−1) compared with placebo (353) fluticasone propionate (138) produced significant (P<0.05) suppression (2.57-fold difference), whereas triamcinolone acetonide (263) did not (1.34-fold difference). Fluticasone
propionate produced a 1.91-fold greater adrenal suppression than triamcinolone acetonide (95% CI 1.10 to 3.33). Individual
subjects with abnormally low 0800 hours cortisol values <150 nmol · l−1 (<5.4 μg/dl) were n=4 for fluticasone propionate and n=0 for triamcinolone acetonide. Overnight urinary cortisol/creatinine ratio (geometric mean, nmol/mmol) did not show any difference
between fluticasone propionate (1.48) and triamcinolone acetonide (1.60), with both producing significant suppression versus
placebo (4.01): triamcinolone acetonide 2.50-fold difference (95% CI 1.45–4.24); fluticasone propionate 2.71-fold difference
(95% CI 1.57–4.69).
Conclusion: Fluticasone propionate 1.625 mg/day (pMDI) produced an approximately two-fold greater adrenal suppression of 0800 hours
plasma cortisol than triamcinolone acetonide 1.60 mg per day (Oral Inhaler) when given twice daily, and one third of subjects
with fluticasone had abnormally low 0800 hours cortisol values <150 nmol · l−1 (<5.4 μg · dl−1). There were no differences between the drugs for urinary cortisol excretion. Further dose-ranging studies are required at
steady-state in asthmatic subjects in order to see whether differences occur at lower doses on the steep part of the dose–response
curve for both plasma and urinary cortisol suppression.
Received: 28 January 1997 / Accepted in revised form: 11 April 1997 相似文献
8.
Chládek J Simková M Vanecková J Hroch M Chládkova J Martínková J Vávrová J Beránek M 《European journal of clinical pharmacology》2008,64(4):347-355
Objective We assessed the effect of folic acid (FA) on the pharmacokinetics and pharmacodynamics of low-dose oral methotrexate (MTX)
during the remission-induction phase of psoriasis treatment.
Methods In a 32-week, open-label, two-way cross-over study, patients (n = 20, seven men, aged 35–70 years) with moderate-to-severe plaque psoriasis were randomly assigned to receive MTX plus FA
(20 mg/week) for 16 weeks followed by MTX monotherapy (three doses of MTX separated by 12-h intervals once a week) for an
additional 16 weeks (treatment arm A, n = 10) or to receive the opposite sequence of treatments (arm B, n = 10). Dosing of MTX was individualised with the help of pre-study evaluation of plasma MTX pharmacokinetics. The Psoriasis
Area and Severity Index (PASI), biochemistry and haematology tests and erythrocyte concentration of MTX polyglutamates (MTXPG)
were evaluated throughout the study.
Results In arms A and B, the mean (range) concentrations of MTXPG (nmol/L) were comparable [week 16: 96.2 (32.0–157) vs. 111 (73.7–175),
P = 0.32; week 32: 103 (55.8–173) vs. 83.6 (27.4–129), P = 0.24]. After 16 weeks, the mean±SEM PASI decreased from 20.1 ± 2.1 to 8.8 ± 1.3 in arm A, while a greater reduction from
27.2 ± 2.1 to 5.1 ± 1.0 occurred in arm B (P < 0.001). Positive correlations were found between the percent improvement in PASI at week 16 and the ratios of the concentration
of MTXPG to plasma folate (rho = 0.59, P = 0.008) or RBC folate concentration (rho = 0.56, P = 0.013). Due to an accelerated decline in PASI in arm A and a trend to its worsening in arm B after crossing over of treatments,
the mean absolute PASI scores in both arms were comparable at week 32.
Conclusion The antipsoriatic effect of MTX during the remission-induction phase of treatment is influenced by folate status and may be
significantly less if combined treatment with FA is used, irrespective of pre-treatment folate levels. The individual tailoring
of MTX dosing needs further attention because the mean percent PASI improvement from baseline was 83% and the inter-patient
variability in response was low after 16 weeks of monotherapy with MTX. 相似文献
9.
Rationale Smokers have weak positive expectancies for nicotine replacement therapies relative to smoking (Juliano and Brandon, Nicotine Tob Res, 6:569–574, 2004).
Objectives This study investigated if a manipulation designed to alter expectancies for the nicotine patch was effective in increasing
positive expectancies for the patch and influencing smoking cessation outcomes during a 2-day abstinence period.
Materials and methods Smokers (n = 72) were randomly assigned to receive information that emphasized either patch benefits (n = 25) or standard patch information including side effects (n = 25). Participants wore placebo patches but were told that the patches contained nicotine. A control condition (n = 22) was informed that they received placebo patches while given standard patch information to independently test the effect
of the nicotine-dose instructional set on abstinence outcomes.
Results Benefits information significantly increased positive expectancies for the patch and promoted positive mood during the abstinence
period relative to the side effects information. Nicotine-dose instructions resulted in fewer lapsed cigarettes and higher
ratings of patch helpfulness than placebo instructions. In particular, women’s smoking behavior appeared to be more influenced
by nicotine instructions than that of men.
Conclusions The results of this preliminary study suggest that information provided to smokers about patch effects and nicotine content
may influence behavioral and subjective outcomes of patch use. 相似文献
10.
Rationale: The effects of caffeine, especially caffeinated coffee, on human performance have been extensively studied. However, few studies
have been naturalistic representations of how tea/coffee is normally consumed in terms of dose and time of consumption. Objectives: This study investigated the effects of day-long consumption of tea, coffee and water on cognitive and psychomotor performance,
and sleep quality at night. Methods: Thirty healthy volunteers received equal volume drinks equivalent to either 1 or 2 cups of tea (containing 37.5 mg or 75
mg caffeine), or coffee (75 mg or 150 mg caffeine), or water, in a randomised five-way crossover design. Drinks were administered
on four occasions during the day (0900, 1300, 1700 and 2300 hours). A psychometric battery consisting of critical flicker
fusion (CFF), choice reaction time (CRT) and subjective sedation (LARS) tests, was administered pre-dose and at frequent time
points post-dose. The Leeds Sleep Evaluation Questionnaire (LSEQ) was completed each morning and a wrist actigraph was worn
for the duration of the study. Results: Caffeinated beverages maintained CFF threshold over the whole day (P<0.05), independent of caffeine dose or beverage type. During the acute phase of beverage ingestion, caffeine significantly
sustained performance compared to water after the first beverage for CFF and subjective sedation (P<0.05), and after the second beverage for the Recognition component of the CRT task (P<0.05). Additionally, there were significant differences between tea and coffee at 75 mg caffeine after the first drink. Compared
to coffee, tea produced a significant increase in CFF threshold between 30 and 90 min post-consumption (P<0.01). However, following the second beverage caffeinated coffee at 75 mg significantly improved reaction time (P<0.05), compared to tea at the same dose, for the Recognition component of the CRT task. Caffeinated beverages had a dose
dependent negative effect on sleep onset (P<0.001), sleep time (P<0.001) and sleep quality (P<0.001). Conclusions: These results indicate that ingestion of caffeinated beverages may maintain aspects of cognitive and psychomotor performance
throughout the day and evening when caffeinated beverages are administered repeatedly. This study also demonstrates that day-long
tea consumption produces similar alerting effects to coffee, despite lower caffeine levels, but is less likely to disrupt
sleep. Other differences between tea and coffee were more subtle, and require further investigation.
Received: 16 February 1999 / Final version: 20 December 1999 相似文献
11.
Katalin Boér István Láng Antonio Llombart-Cussac Inger Andreasson Guillermo L. Vivanco Nick Sanders Gillian M. Pover Elizabeth Murray 《Investigational new drugs》2012,30(2):681-687
Purpose The aim of this Phase II study was to assess the efficacy and safety of vandetanib in combination with docetaxel in patients
with pretreated advanced breast cancer. Methods The primary study objective was to compare the number of progression events in patients receiving once-daily oral vandetanib
(100 mg) in combination with docetaxel (100 mg/m2 iv every 21 days) versus placebo plus docetaxel. Sixty-four patients were randomized to receive study treatment (n = 35, vandetanib; n = 29, placebo). Results A slightly greater number of patients had experienced a progression event by the data cut-off in the vandetanib group (24
[69%]) compared with the placebo group (18 [62%]); HR = 1.19, two-sided 80% CI: 0.79–1.81; two-sided P = 0.59), suggesting that the addition of vandetanib to docetaxel did not affect the risk of disease progression compared
with placebo plus docetaxel. The safety and tolerability profile of the combination therapy reflected those of both drugs
as monotherapy agents. Conclusions In patients with advanced breast cancer, vandetanib plus docetaxel was generally well tolerated. Clinical benefit was not
different to that observed with placebo plus docetaxel. However, due to the small patient number it was not possible to yield
robust results, further research is required to identify predictive factors for patient selection. 相似文献
12.
Oral bambuterol compared to inhaled salmeterol in patients with partially reversible chronic obstructive pulmonary disease 总被引:3,自引:0,他引:3
Cazzola M Calderaro F Califano C Di Pema F Vinciguerra A Donner CF Matera MG 《European journal of clinical pharmacology》1999,54(11):829-833
Objective: There is now good evidence that inhaled salmeterol is an effective agent in chronic obstructive pulmonary disease (COPD),but,
at the present time, data on the effects of bambuterol, which is an oral tarbutaline pro-drug, in patients with COPD are scarce.
Moreover, no comparative study between bambuterol and salmeterol in patients with chronic obstructive airway disorders has
been published. The objective of this research was, consequently, to compare the efficacy and safety of 20 mg oral bambuterol
and 50 μg inhaled salmeterol in patients with partially reversible COPD.
Methods: The speed and length of bronchodilation with 20 mg bambuterol and 50 μg inhaled salmeterol were compared in 16 patients
with partially reversible COPD. The investigation and designed as a double-blind, double-dummy, cross-over, placebo controlled
and randomised study. Lung function (FEV1, FVC) and systemic variables (subjective tremor, heart rate, blood pressure) were monitored prior to the administration of
the drug and for 12 h after each agent on 3 non-consecutive days.
Results: Inhalation of salmeterol induced a significant (P < 0.05) increase of lung function when compared with placebo. In addition, oral bambuterol elicited good bronchodilation,
with its maximum slightly later than for salmeterol. The mean (±SE) AUC0–12 hs for all patients were 3.134 1 ± 0.553 for salmeterol and 1963 1 ± 0.573 for bambuterol. Both AUC0–12 h s were significantly greater than for placebo (P < 0.05), but there was no significant difference (P = 0.077) between the salmeterol and bambuterol AUC0–12 hs. Bambuterol, but not salmeterol, caused tremor in four patients. Moreover, it induced a higher heart rate when compared
with salmeterol at each considered time after the administration of the drug; differences after 9 and 12 h were statistically
significant (P < 0.05).
Conclusion: Both oral bambuterol and inhaled salmeterol resulted in good bronchodilation in patients with stable COPD. However, bambuterol,
but not salmeterol, caused tremor in several subjects and elicited a more pronounced tachycardia.
Received: 11 May 1998 / Accepted in revised form: 13 September 1998 相似文献
13.
Effects of captopril and enalapril on electroencephalogram and cognitive performance in healthy volunteers 总被引:2,自引:0,他引:2
Objective: Captopril and enalapril have been reported to influence cognitive functions and quality of life in hypertensive patients.
Methods: The effects of captopril (12.5 mg and 25 mg) and enalapril (5 mg and 10 mg) administered during 7-day periods on electroencephalogram
(EEG), cognitive functions, and subjective assessments were investigated in healthy males.
Results: Neither captopril nor enalapril influenced EEG and cognitive functions compared with placebo. Captopril 12.5 mg decreased
subjective activity compared with placebo. Enalapril did not alter subjective ratings. Both systolic and diastolic blood pressure
were significantly lower after administration of captopril 25 mg, whereas blood pressure was unaffected by enalapril compared
with placebo.
Conclusion: Our results suggest that central effects of captopril and enalapril were minor and not constant in young healthy men.
Received: 21 September 1998 / Accepted in revised form: 1 February 1999 相似文献
14.
Effect of codeine on oro-cecal transit time in Chinese healthy volunteers in comparison with Caucasian subjects 总被引:1,自引:0,他引:1
Yue QY Hasselström J Svensson JO Säwe J 《European journal of clinical pharmacology》1999,54(11):839-842
Objectives: To evaluate the effect of codeine on oro-cecal transit time (OCTT) in Chinese subjects.
Methods: OCTT was measured with the hydrogen breath test in 12 Chinese healthy volunteers on two occasions: after placebo and after
a single oral dose of codeine 50 mg. Codeine and its metabolites in urine were measured by HPLC. The Results of this study
were compared with those previously obtained from Caucasian subjects.
Results and conclusion: The mean OCTT increased significantly after a single oral dose of codeine 50 mg [2.6 (1.2) h] compared with placebo [1.9 (0.6) h]
in the Chinese subjects (P = 0.05). The increase in OCTT after codeine was similar in the Caucasian [0.9 (0.8) h] and in the Chinese subjects [0.7 (0.9) h].
However, the Chinese subjects had a significantly longer OCTT after placebo [1.9 (0.6) h] compared with the Caucasian subjects
[1.3 (0.6) h, P < 0.05], possibly due to different environmental factors.
Received: 20 April 1998 / Accepted in revised form: 10 August 1998 相似文献
15.
Rationale Serotonergic pharmacological challenges have failed to produce consensual results in patients with obsessive–compulsive disorder
(OCD), suggesting a heterogeneous 5-hydroxytryptamine (5-HT) activity in this disorder.
Objectives The aim of this study was to compare the neuroendocrine response to a serotonergic challenge in OCD patient responders (RP)
and nonresponders (NR) to serotonin reuptake inhibitors treatment and healthy volunteers.
Materials and methods Thirty OCD treatment NR, 30 RP, and 30 controls (CN) matched for sex and age were included. Each subject received 20 mg of
intravenous citalopram. Prolactin, cortisol, and growth hormone plasma concentration were measured at times—20, 0, 20, 40,
60, 80, 100, 120, 140, and 160 min after the onset of citalopram infusion.
Results Citalopram did not induce anxiety or OCD symptoms in patients. Citalopram was associated with stronger prolactin response
in the CN group (maximal percentage variation [max%Δ] = 65.76 ± 105.1) than in NR (max%Δ = 17.41 ± 31.06) and RP groups (max%Δ = 15.87 ± 31.71;
p = 0.032; Friedman χ
2 = 6.87; df = 2). On the other hand, cortisol response did not differ between CN and RP groups and was blunted in the NR group (NR max%Δ = 20.98 ± 58.14
vs RP max%Δ = 47.69 ± 66.94; CN max%Δ = 63.58 ± 88.4; p = 0.015; Friedman χ
2 = 8.60; df = 2).
Conclusions Compared to CN, both treatment RP and NR patients showed blunted prolactin response to citalopram, but only NR patients showed
an attenuated cortisol response, suggesting a more disrupted central serotonergic transmission in this group. 相似文献
16.
M. E. Planas C. Gay-Escoda J. V. Bagán J. Santamaría M. Peñarrocha M. Donado J. L. Puerta I. García-Magaz J. Ruíz P. Ortiz 《European journal of clinical pharmacology》1998,53(6):405-409
Objective: To assess the efficacy of metamizol 1 g and 2 g in the relief of pain after surgical extraction of the lower third molar,
and to compare the therapeutic effect with that of ibuprofen 600 mg or placebo.
Methods: A total of 253 patients aged between 18 years and 60 years who had undergone extraction of the lower third molar (types II–IV)
under local anaesthesia, up to a maximum of 108 mg of mepivacaine, were randomly assigned to a single oral dose of a new galenic
form (drinkable vials) of metamizol 1 g (n = 75), metamizol 2 g (n = 72), ibuprofen 600 mg (n = 74) or placebo (n = 32). Pain intensity was evaluated by a 100-mm visual analogue scale. To enter the study, a pain level of 50 mm or more
was required. The duration of the trial was 1 h. Assessments were carried out at 15, 30 and 60 min after treatment.
Results: The analgesic efficacy of metamizol 2 g was significantly better than ibuprofen and placebo with regard to all evaluated
parameters. The values of the pain intensity difference at 15 min, the percentage of patients with a decrease of 50% or more
on the visual analogue scale at 60 min and the sum of pain intensity differences at 60 min showed metamizol 2 g to be significantly
more effective than metamizol 1 g. In general, metamizol 1 g was as effective as ibuprofen 600 mg. The analgesic efficacy
of placebo was significantly lower than that of all active treatments. A lower number of patients treated with metamizol 1 g
(n = 1) or metamizol 2 g (n = 1) needed rescue medication than those given ibuprofen (n = 7) or placebo (n = 5). No serious adverse effects developed and none of the patients had to leave the study for this reason.
Conclusions: The model of the lower third molar, for which the analgesic outcome referred to the first hour after drug administration,
demonstrated that the analgesic efficacy of oral metamizol 2 g was significantly higher than that of ibuprofen 600 mg or placebo.
Metamizol 1 g and ibuprofen 600 mg showed a similar therapeutic effect. All regimens were as well tolerated as placebo.
Received: 6 July 1997 / Accepted in revised form: 6 October 1997 相似文献
17.
Objective: The present study was designed to explore whether digoxin modifies cutaneous vascular responses to an endothelium-dependent
vasodilator (acetylcholine) or to the vasoconstrictor norepinephrine.
Methods: In a double-blind cross-over study 12 healthy subjects received digoxin 0.25 mg twice daily (after adequate loading doses)
or placebo for a total of 11 days. Dose-response curves to iontophoresis of acetylcholine or norepinephrine were constructed
at day 11. Laser Doppler flux (LDF) was measured at the same sites. Mean arterial pressure (MAP) was measured non-invasively
and cutaneous vascular conductance (CVC) was calculated (CVC=LDF/MAP).
Results: Serum concentrations of digoxin were within the therapeutic range [1.3 (0.5) ng · ml−1; mean with (SD)]. Blood pressure and heart rate were significantly lower during supine rest under digoxin treatment [mean
with (SD); minute 10 to 70 of supine rest; systolic blood pressure: 121 (11) mmHg (placebo) vs 116 (11) mmHg (digoxin); P = 0.001; diastolic blood pressure: 63 (6) mmHg vs 58 (8) mmHg; P = 0.007; heart rate: 60 (10) beats · min−1 vs 54 (8) beats · min−1; P = 0.001]. Digoxin also caused significantly higher baseline CVC [169 (25) Perfusion Units (PU) · mmHg−1 (digoxin) vs 109 (14) PU · mmHg−1 (placebo); P = 0.013] and significantly increased the vasoconstriction to norepinephrine iontophoresis. Acetylcholine iontophoresis was
unaltered by digoxin treatment.
Conclusions: Digoxin does not modify the cutaneous vascular response to an administered endothelium-dependent vasodilator. It reduces
resting heart rate, blood pressure and baseline cutaneous blood flow and augments the vasoconstrictive effect of exogenous
norepinephrine. The findings do not support the hypothesis that digoxin lowers diastolic blood pressure through a direct action
on blood vessels.
Received: 23 October 1998 / Accepted in revised form: 3 February 1999 相似文献
18.
Ahokoski O Irjala K Huhtala S Salminen E Scheinin H Huupponen R 《European journal of clinical pharmacology》1999,55(1):27-34
Objective: Novel aromatase inhibitors are developed with requirements of high potency and selectivity for the aromatase enzyme. The
hormonal effects of a new, non-steroidal competitive inhibitor of the aromatase enzyme, MPV-2213ad, were investigated in this
study.
Methods: The study was conducted as a double-blind, placebo controlled phase I study, where 32 healthy male volunteers were randomized
to receive a single oral dose of either 0.3, 3 or 100 mg of MPV-2213ad or placebo. Serum concentrations of estradiol (E2),
testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol and aldosterone were determined from
samples taken 0, 4, 8 h and 12 h during the day of drug administration and 1, 2, 4 and 7 days after drug intake. The individual
diurnal variation of circulating hormone concentrations was determined in all participants at 0, 4, 8 h and 12 h on the day
before drug intake. Specimens for hematological and biochemical analyses were also collected.
Results: A dose-dependent and statistically significant (P < 0.001) decrease in serum E2 concentrations was induced by MPV-2213ad. Lowest mean values were observed 8–12 h after drug administration
and at 24 h the reductions were 10%, 34% and 69% from baseline in the 0.3-mg, 3-mg and 100-mg groups, compared with an 18%
increase in the placebo group. Serum E2 concentrations returned to baseline within 4 days in all study subjects. A significant
increase was observed in the serum concentrations of testosterone (P = 0.016), LH (P = 0.002) and FSH (P < 0.001) after administration of MPV-2213ad. Serum concentrations of cortisol and aldosterone were unaffected by MPV-2213ad.
The drug was well tolerated.
Conclusion: Single oral doses of MPV-2213ad, given to healthy male subjects, induced hormonal effects typical for a specific and selective
inhibitor of the aromatase enzyme. Importantly, this study design with the determination of the diurnal rhythm in the levels
of the corresponding hormones gives additional validity on the results.
Received: 2 June 1998 / Accepted in revised form: 3 October 1998 相似文献
19.
Interethnic and interindividual variabilities of platelet sulfotransferases activity in Italians and Finns 总被引:1,自引:0,他引:1
Brittelli A De Santi C Raunio H Pelkonen O Rossi G Pacifici GM 《European journal of clinical pharmacology》1999,55(9):691-695
Objective: The aim of this investigation was to see whether there was interethnic variability in the platelet activities of catechol-
and phenol sulfotransferases in Italians and Finns.
Methods: The activities of catechol- and phenol sulfotransferases were measured in platelets obtained from 103 Italian and 74 Finnish
individuals. Blood donors were obtained from healthy volunteers free from drugs and without apparent disease. The activities
of catechol- and phenol sulfotransferases were measured with 60 μM dopamine and 4 μM 4-nitrophenol as substrates, respectively
Results: The activity of catechol sulfotransferase was not gender dependent and the median estimates (pmol/min/mg) were 9.10 in Italians
and 6.37 in Finns (P = 0.0018). The activity of phenol sulfotransferase activity was gender dependent in Finns but not in Italians. The median
estimates (pmol/min/mg) were 3.81 in Finnish men and 1.18 in Finnish women (P = 0.0007). In Italian men and women, the median estimates (pmol/min/mg) of phenol sulfotransferase activity were 1.25 and
1.24, respectively (NS).
Conclusion: This study shows that platelet catechol sulfotransferase activity is greater in Italians than Finns and that the activity
of phenol sulfotransferase is gender regulated in Finns but not in Italians. Thus, interethnic differences exist in platelet
sulfotransferases between Italians and Finns.
Received: 16 April 1999 / Accepted in revised form: 20 August 1999 相似文献
20.
Objective: A double-blind, placebo-controlled parallel study was conducted on the effect of mibefradil, both an L- and T-type Ca2+-channel blocker with a more selective blockade of T-type channels, administered once daily for 1 week to normal male subjects,
on blood pressure, intracellular cationic concentrations, sodium-proton exchange rate and 3
H-thymidine incorporation in peripheral blood mononuclear cells (PBMC).
Methods: After a 1-week run-in period on placebo, the subjects (n = 40) were allocated to a placebo or a mibefradil group. Placebo or 50 mg mibefradil was administered once daily in the morning
for 1 week. All subjects were investigated at baseline and after 1 week of placebo or mibefradil administration. Standing
or recumbent blood pressure and heart rate of subjects in the mibefradil group was decreased (P < 0.05 or less) compared with that of subjects in the placebo group.
Results: Decreased (P < 0.001) intracellular free Ca2+ concentration and reduced (P < 0.001) 3
H-thymidine incorporation in the PBMC were observed in the mibefradil-treated subjects. The intracellular sodium, potassium
or magnesium concentration as well as the sodium-proton exchange rate were not changed during mibefradil administration.
Conclusion: The blood pressure lowering action of mibefradil in men is accompanied by a decrease in intracellular free Ca2+ concentration. Mibefradil also reduced the 3
H-thymidine incorporation or de novo DNA synthesis in PBMC by modulating the calcium homeostasis.
Received: 24 June 1998 / Accepted in revised form: 3 October 1998 相似文献