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To assess the normative values of subfoveal choroidal thickness (SFCT) in healthy Turkish subjects using spectral -domain optical coherence tomography (SD-OCT, Spectralis®, Heidelberg Engineering, Germany) and its relationship with age and gender. One hundred sixty-nine emmetropic healthy subjects (84 men; 49.7%, 85 women 50.3%) underwent a detailed ophthalmological examination. The subjects were divided into 5 groups according to age; Group 1 (n = 42): 18-29 years, group 2 (n = 34): 30-39 years, group 3 (n = 33): 40-49 years, group 4 (n = 34): 50-59 years, group 5 (n = 26): 60 years and older. There were statistically significant differences in mean SFCT values among different age groups (p <0.05). Mean SFCT was highest in subjects under 30 years (364.87 ± 71.24 µm) and lowest in subjects over 60 years (261.25 ± 52.39 µm). There was a statistically significant negative correlation be tween age and SFCT values (r= -0.52, p< 0.001). Slope of change in SFCT over time in the subjects was -2.59 µm per year. When all subjects were evaluated, the mean SFCT value was 322.73 ± 64.00 µm in men and 310.47 ± 60.11 µm in women (p= 0.34). Except group 4, SFCT did not differ between men and women. SFCT decreases with aging and sex does not seem to alter the measurements. Our normative data according to age groups and gender might be used to demonstrate SFCT changes in various retinal and choroidal diseases in Turkish population. [ABSTRACT FROM AUTHOR]

This multiple-ascending-dose study investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of ponesimod, an S1P1 receptor modulator and a potential new treatment for autoimmune diseases. In part A, 10 healthy male and female subjects received once daily oral doses of ponesimod (5, 10, or 20 mg) or placebo for 7 days. Sinus bradycardia and, in some subjects, atrioventricular (AV) block occurred primarily on the first day of dosing, as desensitization developed to ponesimod-induced heart rate (HR) reduction and PR-prolongation. This elicited the design of an up-titration schedule in 17 subjects to a dose of 40 mg in part B. The up-titration regimen reduced HR and PQ/PR effects. Reported adverse events were mainly related to the cardiac and respiratory systems. Respiratory effects increased with higher doses. Ponesimod multiple-dose pharmacokinetics were slightly more than dose-proportional and characterized by a time to maximum concentration and an elimination half-life varying from 2.5 to 4.0 hours and 30.9 to 33.5 hours, respectively, and an accumulation of about 2.3-fold. Ponesimod caused a dose-dependent sustained decrease in total lymphocyte count, reversible within 7 days of discontinuation. A pharmacokinetic-pharmacodynamic model enabled comparing day 1 and steady-state conditions. These results warrant further investigation of ponesimod in patients. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of food on the oral bioavailability of preladenant, a novel adenosine A2A receptor antagonist. This open-label, randomized, single-dose, 2-way crossover study evaluated the effects of a high-fat, high-calorie meal on the pharmacokinetics of preladenant and its metabolite (SCH434748) following oral administration of a single 25-mg preladenant capsule to 24 healthy subjects. When administered with food, the time of maximum concentration (Tmax) of preladenant was prolonged compared with administration in the fasting state. Whereas Tmax was increased from 0.9 hours to 2.6 hours and maximum concentration (Cmax) was decreased (from 212 ng/mL to 128 ng/mL), the extent of absorption (area under the plasma concentration–time curve from time 0 to time of final quantifiable sample, or AUC[tf]) was unaffected by the meal. Similarly, SCH434748 Tmax was prolonged in the fed state, and Cmax decreased from 43.7 ng/mL to 28.6 ng/mL. The assessment of AUC[tf] and area under the plasma concentration–time curve from time 0 to infinity [AUC[I]] together suggests that the AUC for the metabolite remained unchanged. No serious, significant, or unexpected adverse events occurred. In summary, food delays absorption and reduces peak exposure (Cmax) but does not alter the extent of preladenant exposure (AUC). These small changes are unlikely to be of clinical importance. A single 25-mg dose of preladenant is safe and well tolerated in healthy subjects under both fed and fasting conditions. [ABSTRACT FROM PUBLISHER]

In the current literature, there is only a small number of studies that have evaluated the utility of point share wave elastography for pancreatic assessment. Objective: To assess the feasibility of Virtual Touch Quantification (VTQ) elastography for pancreas assessment, as well as the mean pancreatic stiffness values in healthy subjects. Material and method: We included 70 subjects (52.8% women, 47.2% men, average BMI=25.9±4.9 kg/m2, average age 46.8±18.4 years) with a normal pancreatic ultrasound aspect and with no history of pancreatic disease or diabetes, in whom elastography measurements were performed with a Siemens Acuson S2000 Virtual Touch ultrasound system (Siemens AG, Erlangen, Germany) using a 4CI transducer. For each patient, 10 valid VTQ measurements of the pancreatic parenchyma were performed under fasting conditions. Reliable measurements were defined as a median value of ten pancreas stiffness measurements with a success rate ≥60% and an interquartile range interval <30%. Results: Out of 70 subjects, reliable measurements were acquired in 61 subjects (87.1%) by means of VTQ elastography. The mean pancreas stiffness values in healthy subjects was 1.26 m/s ± 0.1 m/s, CI 95% (1.24-1.28). There were no significant differences between the mean pancreas stiffness in men vs. women 1.25 m/s ± 0.09 m/s, CI 95% (1.21-1.28) vs. 1.28 m/s ± 0.1 m/s CI 95% (1.25-1.31) (p=0.103). Conclusion: VTQ can be a useful tool for pancreas quantification characterized by a good feasibility (87.1%) in healthy subjects. The mean pancreas stiffness values in healthy individuals was 1.26 m/s ± 0.1m/s. [ABSTRACT FROM AUTHOR]

Aims: Serelaxin is a recombinant form of human relaxin-2 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (PK) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin., Methods: This was an open-label, parallel group study (NCT01433458) comparing the PK of serelaxin following a single 24 h intravenous (i.v.) infusion (30 μg kg(-1)  day(-1) ) between patients with mild, moderate or severe hepatic impairment (Child-Pugh class A, B, C) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non-compartmental PK parameters [including area under the serum concentration-time curve AUC(0-48 h) and AUC(0-∞) and serum concentration at 24 h post-dose (C24h )] were compared between each hepatic impairment group and healthy controls., Results: A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady-state at 12-24 h and then declined following completion of infusion, with a mean terminal half-life of 7-8 h. All PK parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment-related antibodies developed during this study., Conclusions: The PK and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48 h i.v. infusion in patients with hepatic impairment., (© 2014 The British Pharmacological Society.)