Drug and Alcohol Rehabilitation: Cobicistat-Boosted Elvitegravir-Based Fixed-Dose Combination Antiretroviral Therapy for HIV Infection.

Cobicistat-boosted elvitegravir-based fixed-dose combination antiretroviral therapy for HIV infection.

Filed under: Drug and Alcohol Rehabilitation

Drugs Today (Barc). 2012 Dec; 48(12): 765-71
Temesgen Z

A fixed-dose co-formulated antiretroviral drug containing elvitegravir, a new integrase strand transfer inhibitor, boosted by a novel pharmacokinetic enhancer cobicistat, and further containing the nucleoside pair of tenofovir and emtricitabine was recently approved by the U.S. Food and Drug Administration as a single-tablet, once-a-day treatment of HIV-1 infection in antiretroviral therapy-naive adults. This drug was found to be noninferior to two currently preferred antiretroviral regimens in clinical practice in two large, 48-week, phase III studies. Renal adverse effects limit its use to those with creatinine clearance > 70 mL/min; its considerable drug interaction potential requires care and attention when used. Nevertheless, the availability of this fixed-dose combination product is an important progress in the management of HIV infection for a number of reasons: It provides a third option for a one-pill, once-a-day antiretroviral regimen; it is the first such regimen that is not based on a non-nucleoside reverse transcriptase inhibitor; and it provides an alternative to ritonavir for the pharmaco-enhancement of other antiretroviral drugs.
HubMed – drug

Aclidinium bromide for the treatment of chronic obstructive pulmonary disease.

Filed under: Drug and Alcohol Rehabilitation

Drugs Today (Barc). 2012 Dec; 48(12): 757-63
Joos GF

Inhaled aclidinium bromide has recently been approved by the European Medicines Agency and the U.S. Food and Drug Administration for the maintenance bronchodilator treatment to relieve symptoms of patients with chronic obstructive pulmonary disease (COPD). Aclidinium bromide is a competitive muscarinic receptor antagonist with kinetic selectivity for the muscarinic M(3) receptor and with a long duration of action. It is rapidly hydrolyzed in human plasma, and its metabolites have no activity on muscarinic receptors. Initial phase I and II studies in patients with COPD indicated that aclidinium bromide 200 ?g o.d. had a bronchodilator activity up to 24 hours. However, in subsequent phase III studies, the bronchodilator effect at 24 hours was found to be suboptimal. Phase III trials using 200 and 400 ?g b.i.d. have subsequently reported both clinical significant bronchodilator activities and improved patient-reported outcomes such as quality of life and dyspnea. Aclidinium bromide was also found to be safe and the anticholinergic side effects were reported to be low.
HubMed – drug

HSP90 inhibitor antagonizing MIF: The specifics of pleiotropic cancer drug candidates.

Filed under: Drug and Alcohol Rehabilitation

Oncoimmunology. 2012 Nov 1; 1(8): 1425-1426
Schulz R, Dobbelstein M, Moll UM

Constitutively stabilized HSP90 client proteins are crucial for cancer cell survival and proliferation. Thus, despite-or perhaps because of-their pleiotropic effects on variety of critical oncoproteins, HSP90 inhibitors represent a promising new class of anticancer drugs. We identified MIF as an essential HSP90 client protein in a murine model of Her2-overexpressing breast cancer.
HubMed – drug

Studying the role of the immune system on the antitumor activity of a Hedgehog inhibitor against murine osteosarcoma.

Filed under: Drug and Alcohol Rehabilitation

Oncoimmunology. 2012 Nov 1; 1(8): 1313-1322
Paget C, Duret H, Ngiow SF, Kansara M, Thomas DM, Smyth MJ

Recent evidence demonstrates that the efficacy of conventional anticancer therapies including chemotherapy requires a functional immune system. Here, we addressed the possibility that the antitumor effect of a selective Smoothened antagonist and Hedgehog (Hh) pathway inhibitor (LDE225), a promising anticancer drug, might at least partially depend on the immune system. To this aim, we used tumor cell lines derived from a murine model of radiation-induced osteosarcoma. In vitro treatment of osteosarcoma cells with LDE225 resulted in a decreased ability of tumor cells to proliferate, but had no effect on their viability. Flow cytometry analysis demonstrated that LDE225-treatment did not detectably modulate the immunogenicity of tumor cells. Moreover, LDE225 did not display any pro-apoptotic properties on osteosarcoma cells, highlighting that its antitumor profile mainly derives from a cytostatic effect. Furthermore, calreticulin exposure, a key feature of immunogenic cell death, was not provoked by LDE225, neither alone nor combined with recognized immunogenic drugs. Finally, the oral administration of LDE225 to osteosarcoma-bearing mice did significantly delay the tumor growth even in an immunocompromised setting. These data suggest that inhibiting Hh signaling can control osteosarcoma cell proliferation but does not modulate the immunogenic profile of these cells.
HubMed – drug

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