International journal of clinical pharmacology & toxicology最新文献

Background: Selective Mutism is described as the inability to verbally express oneself in anxiety provoking social situations and may result in awkward social interactions in school-aged children. In this case-report we present the baseline electrophysiological neuroimaging results and after treatment with Sertraline for 6-weeks.

Methods: A 20-channel EEG event-related potential recording was acquired during an internal voice task at baseline prior to the initiation of 50mg of Sertraline and then repeated 6-weeks after treatment with Sertraline. EEG signals were processed for movement, eye-blink, and muscle artifacts and ERP signal averaging was completed. ERPs were analyzed using Standard Low Resolution Brain Electromagnetic Tomography (sLORETA).

Results: At baseline, Sertraline increased the neuronal activation in the middle temporal gyrus and the anterior cingulate gyrus from baseline in the patient following 6-weeks of treatment.

Conclusion: Our findings suggest that electrophysiological neuroimaging may provide a creative approach for personalizing medicine by providing insight to the pharmacodynamics of antidepressants.

Introduction: This article seeks to clarify if gender-based differences occur in the pharmacokinetics of metoprolol in the elderly patients. There are a series of physiologic changes that occur in the elderly ranging from decreased hepatic blood flow to increased adiposity causing higher plasma concentrations at therapeutic doses as compared to the healthy young population.

Methods: Population pharmacokinetic modeling were performed using MONOLIX and Monte-Carlo simulations were conducted using MATLAB. The data was based from a previously published dataset where elderly patients, having multiple comorbidities, were administered a 50mg dose of metoprolol.

Results: Metoprolol was modeled using a one-compartment model and resulted in the following population pharmacokinetic parameters: volume of distribution, V=38L (CV=155%), clearance rates, CL-Men=105L/hour and CL-Women=59.1L/hour (38%), time lag, Tlag=0.469 hour (CV=17%), and the absorption rate constant, Ka=0.235 hr^-1 (CV=23%).

Conclusion: Gender stratified doses resulting in an equivalent systemic metoprolol exposure in geriatric patients have been identified. Metoprolol doses resulting a similar AUC in a healthy young male administered 50mg tablet were 15mg for geriatric women and 25mg for geriatric men. Further, Metoprolol doses of 25mg for geriatric women and 50mg for geriatric men resulted in an equivalent AUC to a healthy young males dosed with a 100mg tablet. A 15mg Metoprolol tablet may need to be compounded to account for the gender differences in Metoprolol pharmacokinetics.

The renin-angiotensin system (RAS) is a hormonal cascade that acts together to regulate blood pressure. Angiotensin II (Ang II) is the major octapeptide of RAS and mediates its cellular and physiological actions by acting on AT₁ and AT₂ receptor. Most of the cellular and physiological actions of Ang II such as cellular growth and proliferation, vasoconstriction, antinatriuresis and increase in blood pressure are mediated via AT₁ receptor. The functions associated with the AT₂ receptors are less studied, in part, due to its lower expression in adult tissues. However, AT₂ receptor has been suggested as functional antagonist of AT₁ receptors and thereby opposes the actions of Ang II mediated via AT₁ receptor. Thus, the activation of AT₂ receptors has been shown to cause vasodilatation, natriuresis and decrease in blood pressure. After the discovery of the AT₂ receptor in various parts of the kidney, including in proximal tubules, there has been an interest in establishing a link between the renal AT₂ receptor, renal Na-excretion and blood pressure regulation. Earlier, we have reported that activation of renal AT₂ receptors increases urinary Na excretion in obese Zucker rats, in part via inhibiting Na⁺/K⁺- ATPase (NKA) activity and stimulating nitric oxide/cGMP pathway in the proximal tubules. An impaired pressure natriuresis and increased AT₁ receptor function is believed to be the cause of hypertension in obese Zucker rats and other animal models of obesity. In this review, we are focussing on the role of renin angiotensin system especially AT₂ receptors in obesity associated hypertension.