Pharmacokinetic and Pharmacodynamic (PK-PD) Studies of Cardiovascular Drugs (U01)

The objectives of this project are to conduct a prospective PK/PD study in hypertensive patients to link the PK profiles to the time-course of PD activity of metoprolol, therefore, to identify the key product attributes and patient factors that may impact the therapeutic equivalence of metoprolol products. The specific objectives of the study were to: 1) Evaluate the PK-PD relationship; 2) Evaluate the effect of treatment (before and after switching metoprolol products) on the PK-PD relationship; 3) Evaluate the effect of pH variation in the population and rate of delivery on the PK-PD relationship; 4) Evaluate the effect of CYP2D6 phenotype on the PK-PD relationship; Detailed Description: Additional details regarding the study objectives are listed below: A prospective, randomized crossover trial design is suggested, i.e., switching over to a different metoprolol product at the same dose level as the prior one. The study should use a combination of products having different shapes of PK profiles. Simultaneous collections of PK and PD samples (before and after switch) at steady state are recommended to link PK profiles to PD effect. The selection of appropriate PD endpoint(s) has to be well justified. The study should enroll CYP2D6 extensive and poor metabolizers to assess the CYP2D6 phenotype impact on the PK profiles and PD activity of metoprolol extended release tablets. The study should evaluate the pH variations of the population and its impact on the PK profile...
Source: Grants.gov - Category: Research Tags: Health Science and Technology and other Research and Development Source Type: funding

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es MA Abstract The sympathetic nervous system (SNS) regulates body functions in normal and pathological conditions and is characterized by the presence of a neuroplastic phenomenon, termed ganglionic long-term potentiation (gLTP). In hypertension, either in spontaneously hypertensive rats (SHR) or in humans, sympathetic hyperfunction, such as elevated SNS outflow and changes in synaptic plasticity have been described. Because enhanced SNS outflow is detected in the hypertensive stage and, more importantly, in the prehypertensive phase of SHR, here we explored whether synaptic plasticity, particularly gLTP, was mod...
Source: Neural Plasticity - Category: Neurology Authors: Tags: Neural Plast Source Type: research
s N Abstract Hypertension is the first modifiable vascular risk factor accounting for 10.4 million deaths worldwide; it is strongly and independently associated with the risk of stroke and is related to worse prognosis. In addition, hypertension seems to be a key player in the implementation of vascular cognitive impairment. Long-term hypertension, complicated or not by the occurrence of ischemic stroke, is often reviewed on its vascular side, and parenchymal consequences are put aside. Here, we sought to review the impact of isolated hypertension or hypertension associated to stroke on brain atrophy, neuron conne...
Source: Neural Plasticity - Category: Neurology Authors: Tags: Neural Plast Source Type: research
Effect of Body Weight Change on Blood Pressure in a Japanese General Population with a Body Mass Index ≥ 22 kg/m2. Int Heart J. 2019 Nov 15;: Authors: Itoh H, Kaneko H, Kiriyama H, Nakanishi K, Mizuno Y, Daimon M, Morita H, Yamamichi N, Komuro I Abstract The association between changes in body weight and blood pressure (BP) in overweight people in the general population still remains unclear. We sought to clarify the effect of body weight change on BP using a community-based cohort. We studied 1,170 overweight subjects with a body mass index (BMI) ≥ 22 kg/m2 who underwent health check-ups. Among ...
Source: International Heart Journal - Category: Cardiology Tags: Int Heart J Source Type: research
In this study, we examined the role of SMP30 in pulmonary vasculature using SMP30-deficient mice.We used female SMP30-deficient mice and wild-type littermate (WT) mice at the age of 12 to 18 weeks. The WT and SMP30-deficient mice were exposed to normoxia or hypoxia (10% oxygen for 4 weeks). In normoxia, the right ventricular systolic pressure (RVSP) was not different between the WT and SMP30-deficient mice, but in hypoxia, the RVSP was significantly higher in the SMP30-deficient mice compared to the WT mice (P
Source: International Heart Journal - Category: Cardiology Tags: Int Heart J Source Type: research
Conditions:   Intra Cerebral Hemorrhage;   Hypertension Intervention:   Diagnostic Test: Modified Rankin Scale (mRS) Sponsor:   Mansoura University Hospital Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conclusions: The higher levels of leptin in pregnant women with gestational hypertension may be suggestive of the role of leptin in GH development. As the patients in the GH group had higher BMI, hyperleptinemia may link obesity with gestational hypertension. The significance of leptin as the predictive marker of GH development could be implied. It could be postulated that the higher levels of sICAM-1 in the GH patients, although not statistically significant, could reflect some impairment of the endothelium function occurring in GH regardless of BMI. The comparable adiponectin levels in GH and healthy pregnant patients an...
Source: International Journal of Hypertension - Category: Cardiology Tags: Int J Hypertens Source Type: research
Authors: Wu X, Wang Z Abstract Hypertension is an important global health concern. The relationship between hypertension and socioeconomic status (SES) has been extensively studied. However, the role of SES in hypertension is still controversial, and this kind of study is sorely lacking among Chinese middle-aged and elderly individuals. The data of this study come from the China Health and Retirement Longitudinal Survey (CHARLS) released in May 2017. A total of 21,126 people from all around China, with ages older than 45 years, were enrolled in the questionnaire survey. Hypertension was determined according to the ...
Source: International Journal of Hypertension - Category: Cardiology Tags: Int J Hypertens Source Type: research
Erratum to "Nonpharmacologic Interventions in Prevention and Treatment of Hypertension". Int J Hypertens. 2019;2019:2907675 Authors: Erejuwa OO, Gan SH, Romani AMP, Kamal MA, Nammi S Abstract [This corrects the article DOI: 10.1155/2019/6709817.]. PMID: 31737360 [PubMed - in process]
Source: International Journal of Hypertension - Category: Cardiology Tags: Int J Hypertens Source Type: research
Calcific aortic stenosis (AS) is the most frequent valvular heart disease in high-income countries and the third most frequent cardiovascular disease after hypertension and coronary artery disease. The prevalence of aortic sclerosis (ie, the preclinical stage of AS) is estimated at 25% in the general population older than 65 years and close to 50% in those older than 80 years.1 The prevalence of AS is less than 1% in the population less than 60 years old,2 but increases exponentially to more than 10% in elderly people older than 75 years.
Source: Cardiology Clinics - Category: Cardiology Authors: Tags: Preface Source Type: research
In conclusion, HFD-induced hypertension is not driven by increased sympathetic neurotransmission to MA in male and female Dahl ss rats. PMID: 31731103 [PubMed - in process]
Source: Autonomic Neuroscience - Category: Neuroscience Authors: Tags: Auton Neurosci Source Type: research
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