scholarly journals Pharmacodynamic and pharmacokinetic behavior of landiolol during dobutamine challenge in healthy adults

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Günther Krumpl ◽  
Ivan Ulč ◽  
Michaela Trebs ◽  
Pavla Kadlecová ◽  
Juri Hodisch

Abstract Background To study the pharmacokinetic and -dynamic behavior of landiolol in the presence of dobutamine in healthy subjects of European ancestry. Methods We conducted a single-center, prospective randomized study in 16 healthy subjects each receiving an infusion of dobutamine sufficient to increase heart rate by 30 bpm followed by a 60 min infusion of 10 μg/kg/min landiolol. Results Dobutamine-induced increases in heart rate were stable for at least 20 min before a 60 min landiolol- infusion was started. The dobutamine effects were rapidly antagonized by landiolol within 16 min. A further slight decrease in heart rate during 20–60 min of the landiolol infusion occurred as well. Upon termination of landiolol infusion, heart rate and blood pressure recovered rapidly in response to the persisting dobutamine infusion but did not return to the maximum values before landiolol infusion. The pharmacokinetic parameters of landiolol in presence of dobutamine showed a short half-life (3.5 min) and a low distribution volume (0.3 l/kg). No serious adverse events were observed. Conclusion Landiolol can antagonize the dobutamine-induced increases in heart rate and blood pressure in a fast way. A rapid bradycardic effect until steady-state plasma levels is followed by a slow heart rate reduction. The latter can be attributed to an early desensitization to dobutamine. Consequently, after termination of landiolol, the heart rate did not achieve maximum pre-landiolol values. The pharmacokinetics of landiolol during dobutamine infusion are similar when compared to short- and long-term data in Caucasian subjects. Landiolol in the given dose can thus serve as an antagonist of dobutamine-induced cardiac effects. Trial registration Registration number 2010–023311-34 at the EU Clinical Trials Register, registration date 2010-12-21.

2014 ◽  
Vol 12 (1) ◽  
pp. 55-60 ◽  
Author(s):  
Antônio José Grande ◽  
Valter Silva ◽  
Sérgio Alencar Parra

Objective : To investigate the effectiveness of workplace exercise for employee health by means of health-related physical activity components. Methods : A randomized uncontrolled study with 20 workers was carried out during three months to evaluate a workplace exercise program. The selected outcomes were flexibility, body mass, fat percentage, lean mass, blood pressure, and heart rate. For statistical analysis, the paired t test and the intent-to-treat analysis were used. Results : There was a significant increase in weight, fat percentage, blood pressure, and heart rate. However the clinical significance was 10% in the size of the effect. Conclusion : The changes verified in the outcomes analyzed were not significant; the variables are within normality ranges proposed by academic organizations


2017 ◽  
Vol 17 (2) ◽  
pp. 5-14 ◽  
Author(s):  
Milana Drumond Ramos Santana ◽  
Eli Carlos Martiniano ◽  
Larissa Raylane Lucas Monteiro ◽  
Maria Do Socorro Santos De Oliveira ◽  
Vitor E. Valenti ◽  
...  

AbstractIntroduction: There is an increase in level of stress in the general population because of the social, personal and professional demands. Currently, there are only simple tools that can safely measure this stress such as levels of cortisol and heart rate variability (HRV). Objective: To analyze the relationship between salivary cortisol and the cardiac autonomic modulation. Methods: A total of fifty-one male and female subjects between 18 and 40 years old were evaluated. Saliva collection was achieved for the salivary cortisol dosage. The collection was performed through the SalivetteR tube. After this collection, the median cortisol levels (0.24 ug/dl) were analyzed and the volunteers were divided into two groups: i) cortisol below the mediane ii) cortisol above the median. After this division, each group consisted of 25 volunteers and then was verified the following information: age, gender, weight, height, body mass index (BMI), blood pressure. Shortly thereafter was assessment of cardiac autonomic modulation por meio da HRV. The Polar RS800cx heart rate receiver was placed on the chest of the volunteers, in the vicinity of the distal third of the sternum. The volunteers were instructed to remain in rest with spontaneous breathing in dorsal position for 20 minutes. HRV analysis included geometric, time and frequency domain indices. Results: There were no statistical differences for the two groups regarding systolic and diastolic blood pressure, heart rate, RR intervals or linear and frequency indices for the volunteers. In addition, also there was no correlation the cortisol with the analyzed variables (SAP, p=0.460; DAP, p = 0.270; HR, p = 0.360; RR, p = 0.380; SDNN, p = 0.510; rMSSD, p = 0.660; pNN50, p = 0.820; RRtri, p = 0.170; TINN, p = 0.470; SD1, p = 0.650; SD2, p = 0.500; LF [ms2], p = 0.880; LF [nu], p = 0.970; HF [ms2], p = 0.870; HF [nu], p = 0.960; LF/HF, p = 0.380 Conclusion: Heart rate variability autonomic control was unchanged in healthy subjects with physiological distribution of salivary cortisol levels. There was no association between normal salivary cortisol and resting autonomic regulation of heart rate.


2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Taghi Amiriani ◽  
Vahid Khori ◽  
Ali Davarian ◽  
Niloofar Rajabli ◽  
Mahsa Niknam ◽  
...  

Background: Cirrhosis could lead to a long corrected QT (QTc) interval in a subgroup of patients, but there are spare data on its diurnal variation. Objectives: The present study aimed to determine the diurnal variation of QTc interval and its relationship to heart rate and blood pressure variation during 24-hour Holter-monitoring in non-alcoholic cirrhosis in comparison with the healthy controls. Methods: The study population comprised 15 patients with non-alcoholic cirrhosis and 15 healthy subjects, undergoing 24-hour electrocardiogram (ECG), heart rate, and blood pressure monitoring. The mean QT interval, mean QTc, maximum and minimum QT, QT dispersion (QT disp), heart rate, and mean arterial blood pressure were measured for each person for 24 hours. Liver stiffness measurement (LSM) was performed by FibroScan® 502 machine (EchoSense, Paris, France, 5 MHz). The results were demonstrated as percentages and mean ± SD. P value ≤ 0.05 was considered significant. Results: Mean QTc was significantly higher in cirrhosis (438 ms) than healthy controls (401.7 ms) (P = 0.03). The mean heart rate was significantly different in cirrhotic patients (79.6 ± 2.9/bpm) compared to healthy controls (72.47 ± 2.0/bpm) (P = 0.05). Conclusions: In this study, QTc was prolonged and increased with the severity of cirrhosis, and its diurnal variation in cirrhosis was different from healthy subjects.


2004 ◽  
Vol 96 (6) ◽  
pp. 2333-2340 ◽  
Author(s):  
Tomi Laitinen ◽  
Leo Niskanen ◽  
Ghislaine Geelen ◽  
Esko Länsimies ◽  
Juha Hartikainen

In elderly subjects, heart rate responses to postural change are attenuated, whereas their vascular responses are augmented. Altered strategy in maintaining blood pressure homeostasis during upright position may result from various cardiovascular changes, including age-related cardiovascular autonomic dysfunction. This exploratory study was conducted to evaluate impact of age on cardiovascular autonomic responses to head-up tilt (HUT) in healthy subjects covering a wide age range. The study population consisted of 63 healthy, normal-weight, nonsmoking subjects aged 23–77 yr. Five-minute electrocardiogram and finger blood pressure recordings were performed in the supine position and in the upright position 5 min after 70° HUT. Stroke volume was assessed from noninvasive blood pressure signals by the arterial pulse contour method. Heart rate variability (HRV) and systolic blood pressure variability (SBPV) were analyzed by using spectral analysis, and baroreflex sensitivity (BRS) was assessed by using sequence and cross-spectral methods. Cardiovascular autonomic activation during HUT consisted of decreases in HRV and BRS and an increase in SBPV. These changes became attenuated with aging. Age correlated significantly with amplitude of HUT-stimulated response of the high-frequency component ( r = -0.61, P < 0.001) and the ratio of low-frequency to high-frequency power of HRV ( r = -0.31, P < 0.05) and indexes of BRS (local BRS: r = -0.62, P < 0.001; cross-spectral baroreflex sensitivity in the low-frequency range: r = -0.38, P < 0.01). Blood pressure in the upright position was maintained well irrespective of age. However, the HUT-induced increase in heart rate was more pronounced in the younger subjects, whereas the increase in peripheral resistance was predominantly observed in the older subjects. Thus it is likely that whereas the dynamic capacity of cardiac autonomic regulation decreases, vascular responses related to vasoactive mechanisms and vascular sympathetic regulation become augmented with increasing age.


Epidemiology ◽  
2011 ◽  
Vol 22 ◽  
pp. S39-S40
Author(s):  
Jia-Jang Yang ◽  
Lian-Yu Lin ◽  
Chih-Ming Ma ◽  
Kai-Jen Chuang

2020 ◽  
Vol 15 (1) ◽  
pp. 6-10
Author(s):  
Sadia Afrin Rimi ◽  
Shamima Sultana ◽  
Iffat Rezwana ◽  
Sultana Ferdousi

Background: Tilt table test is used for the last few decades to detect cause in unexplained syncope. The response to tilting may vary physiologically with obesity. Objective: To assess the relationship of BMI to cardiovascular response to tilting. Methods: This experimental study was conducted from March 2019 to Feb 2020 on 90 healthy subjects with different BMI. Fifty one subjects of both gender with BMI 18.5-24.9 kg/m2 were included in the non-obese group and 39 subjects of both gender with BMI of 25-29.9 kg/m2 were included in overweight group and they were further subdivided into male and female. Head up tilting was done for 10 minutes at 600 by using a motorized tilt table. Systolic blood pressure (SBP), diastolic blood pressure (DBP) were recorded by an automatic sphygmomanometer. Heart rate (HR) and peripheral capillary oxygen saturation (SpO2) were measured by a pulse oximeter. For statistical analysis, Independent sample ‘t’ test, Pearson’s correlation test and Chi square tests were applied. Results: Significantly smaller rise of heart rate was observed in overweight males and greater fall of systolic blood pressure was observed in overweight females. Conclusion: This study concluded that over weight is associated with reduced orthostatic tolerance to head up tilt test in both genders. J Bangladesh Soc Physiol. 2020, June; 15(1): 6-10


2020 ◽  
Vol 11 ◽  
Author(s):  
Yinjuan Li ◽  
Lu Qi ◽  
Haihong Bai ◽  
Ying Liu ◽  
Rongxia Fan ◽  
...  

Objective: This study evaluated the pharmacokinetics, safety, and bioequivalence (BE) of two formulations of rasagiline tablets in healthy Chinese subjects under fasting and fed conditions.Methods: An open, randomized, single-dose, double-cycle, two-sequence, self-crossover pharmacokinetic study in healthy Chinese subjects under fasting and high-fat postprandial conditions was performed. A total of 108 healthy subjects (36 in the fasting group and 72 in the postprandial group) were recruited. In each cycle of the study under both conditions, subjects received a single oral dose of 1 mg of a test or reference preparation of rasagiline tablets (1 mg each). A washout period of 3 days was observed. Blood samples were obtained up to 10 h post-intake. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0–t and AUC0–∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters.Results: The 90% confidence interval (CI) of the geometric mean ratio (GMR) of the test drug vs. the reference drug for rasagiline was 94.16–105.35% for the AUC0–t under fasting conditions and 99.88–107.07% under postprandial conditions. The 90% CIs for the AUC0–∞ were 93.55–105.01% and 99.59–107.05% under fasting and postprandial conditions, respectively. The 90% CIs for the Cmax were 88.26–108.46% and 89.54–118.23% under fasting and postprandial conditions, respectively. The 90% CIs for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80–1.25) for BE. In this BE study, there were no serious adverse events (AEs).Conclusion: BE between the test and the reference products was established in both fasting and postprandial conditions. The two formulations of rasagiline showed good tolerability and a similar safety profile.Clinical Trial Registration:chinaDrugtrials.org.cn, identifier CTR20181466.


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