Posaconazole is a triazole antifungal in development for the treatment of invasive fungal infections. The authors evaluated the pharmacokinetics and safety of posaconazole in healthy subjects and in those with mild (CL(CR) = 50-80 mL/min), moderate (CL(CR) = 20-49 mL/min), and severe chronic renal disease (CL(CR) <20 mL/min; receiving outpatient hemodialysis) (n = 6/group). Subjects received one 400-mg dose of posaconazole oral suspension with a standardized high-fat breakfast. For hemodialysis-dependent subjects, this dose was given on a nonhemodialysis day, and a second 400-mg dose was given 6 hours before hemodialysis. Blood samples were collected before dose and up to 120 hours postdose. For hemodialysis-dependent subjects following the second dose, additional samples (predialyzed and postdialyzed) were collected before, during, and after dialysis. There was no correlation between posaconazole pharmacokinetics and mild to moderate renal disease; the slopes of the linear regressions for creatinine clearance versus posaconazole AUC, C(max), CL/F, and t1/2 values were not significantly different from zero (P > .130). Mean CL/F values before and during hemodialysis were comparable. Furthermore, the difference in the predialyzed and postdialyzed posaconazole concentrations was only approximately 3%, supporting that posaconazole was not removed by hemodialysis. Protein binding was similar in all groups (approximately 98%) and was unaffected by hemodialysis. Posaconazole was generally well tolerated. One patient had elevated liver function test results that were not present at baseline and were thought to be possibly related to posaconazole. Results of this single-dose study indicate that dosage adjustments for patients with varying degrees of renal disease are not required.

Analysis of microcirculation through angiography indices in patients with and without HFPEF has led to assess that the HFPEF population has a greater involvement of microcirculation than patients without HFPEF.

ET-1 plasmatic levels significantly influence the cardiovascular and cerebrovascular risk profile, beyond traditional cardiovascular risk factors and preclinical carotid atherosclerosis.

During the last 20 years, the management of heart failure has significantly improved by means of new pharmacotherapies, more timely invasive treatments and device assisted therapies. Indeed, advances in mechanical support, namely with the development of more efficient left ventricular assist devices (LVAD), and the total artificial heart have reduced mortality and morbidity in patients with end-stage heart failure awaiting for transplantation. However, the transplant cannot be the only solution, due to an insufficient number of available donors, but also because of the high number of patients who are not candidates for severe comorbidities or advanced age. New perspectives are emerging in which the VAD is no longer conceived only as a “Bridge to Transplant”, but is now seen as a destination therapy. In this review, the main VAD classification, current basic indications, functioning modalities, main limitations of surgical VAD and the total artificial heart development are described.

Clinical Pharmacology & Therapeutics (2003) 73, P45–P45; doi: