Insulin Degludec: A Long-Acting Modern Insulin Analogue With a Predictable Pharmacokinetic/pharmacodynamic Profile.

Insulin degludec: a long-acting modern insulin analogue with a predictable pharmacokinetic/pharmacodynamic profile.

Drugs Today (Barc). 2013 Jun; 49(6): 387-397
Rendell M

Insulin degludec is, like insulin detemir, a product of coupling of Des-B30 threonine insulin to fatty acid side chains. After injection, degludec self associates, precipitating in subcutaneous tissue. There is a continuous and highly predictable slow dissociation of insulin monomers from this depot; insulin levels rise immediately reaching tmax at 10-12 hours, followed by a slow decline with a t½ of 17-21 hours, roughly double the duration of action of insulin glargine. An important property of degludec not shared by glargine is miscibility with rapid-acting insulin. Although the effect of coadministered insulin aspart is somewhat blunted by coformulation with degludec, a preparation of 70% degludec and 30% aspart has predictable pharmacodynamics. Daily administration of degludec has glucose-lowering benefits not different from those of glargine, with purportedly less hypoglycemia. Although degludec is approved and marketed in Europe under the brand name Tresiba®, the U.S. Food and Drug Administration, in a surprising development, challenged the assertion of lower tendency to hypoglycemia with degludec, and, more importantly, raised concerns that degludec may have a higher cardiovascular risk than glargine. Only a long-term study in a large patient population can resolve these questions. However, release of degludec for marketing to appropriate patients should proceed while awaiting the results of such a study. HubMed – drug


Dabrafenib in the treatment of advanced melanoma.

Drugs Today (Barc). 2013 Jun; 49(6): 377-385
Medina T, Amaria MN, Jimeno A

Advanced melanoma has long been a challenging malignancy to treat due to a relative paucity of efficacious therapeutic options. However, the identification of activating BRAF mutations in approximately 50% of patients with cutaneous melanoma has ushered in the era of targeted therapy for melanoma patients. Similar to the first-in-class selective serine/threonine-protein kinase B-raf inhibitor vemurafenib, dabrafenib is highly efficacious in melanoma patients with BRAF V600E mutations, with response rates of approximately 50% and progression-free survival of 6 months. There is data to suggest that dabrafenib not only shows activity in V600E-mutated melanoma, but also in non-V600E BRAF-mutated disease such as V600K. There is also early data to suggest that dabrafenib is effective in controlling metastases in the brain. Combining dabrafenib with the selective mitogen-activated protein kinase kinase (MEK) inhibitor trametinib has been effective in improving both the progression-free survival and overall survival of melanoma patients over those patients treated with dabrafenib alone. Dabrafenib is still being evaluated in several clinical trials in melanoma as well as a variety of other solid tumors with BRAF mutations. The U.S. Food and Drug Administration has recently approved dabrafenib as a single agent for the treatment of unresectable or metastatic melanoma in adult patients with BRAF V600E mutation. HubMed – drug


Canagliflozin for the treatment of type 2 diabetes.

Drugs Today (Barc). 2013 Jun; 49(6): 363-376
Babu A

Canagliflozin, an oral inhibitor of sodium/glucose cotransporter 2 (SGLT2) in the kidneys, leads to glucosuria and provides a unique mechanism to lower blood glucose levels in diabetes. It corrects a novel pathophysiological defect, has an insulin-independent action, reduces HbA1c by 0.5 to 1.1%, promotes weight loss, has a low incidence of hypoglycemia, complements the action of other antidiabetic agents, can be used at any stage of diabetes and appears to be safe in patients with compromised renal function. Due to side effects such as urinary tract and genital infections and decrease in blood pressure, proper patient selection for drug initiation and close monitoring will be important. Results of ongoing cardiovascular safety trials are important to determine the risk-benefit ratio. Canagliflozin is the first oral SGLT2 inhibitor approved in the U.S. market and it represents a promising approach for the treatment of diabetes in this era of increasing obesity. HubMed – drug


Bedaquiline for the treatment of pulmonary, multidrug-resistant tuberculosis in adults.

Drugs Today (Barc). 2013 Jun; 49(6): 353-361
Gras J

After AIDS, tuberculosis (TB) is the leading killer worldwide due to a single infectious agent. Recently, drug-resistant strains of Mycobacterium tuberculosis elicited even more severe versions of TB. Bedaquiline inhibits mycobacterial ATP synthase. It shows potent and selective activity in vitro against M. tuberculosis, and in vivo against murine models of TB. Bedaquiline can be combined with antituberculosis and antiretroviral agents. The product displays good oral absorption, has a long terminal half-life and is metabolized mainly by cytochrome P450 3A4. In a phase II clinical trial in patients with multidrug-resistant TB, bedaquiline (combined with the standard five-drug, second-line TB regimen), showed a time to 50% culture negative conversion of 78 days, with 81.0% and 52.4% efficacy at weeks 24 and 104, respectively. Bedaquiline was generally safe and well tolerated. At the end of 2012, the U.S. Food and Drug Administration approved bedaquiline (Sirturo®) as part of a combination therapy to treat adults with multidrug-resistant TB. HubMed – drug