However, other research indicates that the toxic effects of DES may simply be due to overactivation of the ERs. In contrast to estradiol, the hydroxyl groups of DES do not undergo oxidation into an estrone-like equivalent.The elimination half-life of DES is 24 hours. The metabolites of DES are excreted in urine and feces. Chemistry
DES belongs to the stilbestrol (4,4-dihydroxystilbene) group of compounds. It is a nonsteroidal open-ring analogue of the steroidal estrogen estradiol. DES can be prepared from anethole, which also happens to be weakly estrogenic. Anethole was demethylated to form anol and anol then spontaneously dimerized into dianol and hexestrol, with DES subsequently being synthesized via structural modification of hexestrol. As shown by X-ray crystallography, the molecular dimensions of DES are almost identical to those of estradiol, particularly in regards to the distance between the terminal hydroxyl groups. History
Synthesis
DES was first synthesized in early 1938 by Leon Golberg, then a graduate student of Sir Robert Robinson at the Dyson Perrins Laboratory at the University of Oxford. Golbergs research was based on work by Wilfrid Lawson at the Courtauld Institute of Biochemistry, (led by Sir Edward Charles Dodds at Middlesex Hospital Medical School now part of University College London). A report of its synthesis was published in Nature on 5 February 1938.DES research was funded by the UK Medical Research Council (MRC), which had a policy against patenting drugs discovered using public funds. Because it was not patented, DES was produced by more than 200 pharmaceutical and chemical companies worldwide.
There is no clinically significant activity against Gram-negative bacteria.Two trials, DISCOVER 1 and DISCOVER 2, demonstrated noninferiority of dalbavancin compared to vancomycin/linezolid in the treatment of ABSSSI. Patients were randomly assigned to receive two doses of dalbavancin on days 1 and 8, or to receive intravenous vancomycin for at least 3 days with the option of switching to oral linezolid to complete 10 to 14 days of therapy. Investigators assessed the cessation of spread of infection-related erythema and the absence of fever at 48 to 72 hours as the primary endpoint and found that once-weekly dalbavancin was as effective as twice-daily intravenous vancomycin followed by oral linezolid. This once-weekly dosing regimen may offer an advantageous treatment option compared to daily or twice-daily dosing. Contraindications
Hypersensitivity to dalbavancin can occur, causing issues such as skin reactions or anaphylaxis. Caution is advised for patients with known hypersensitivity to other glycopeptides. There is currently no data on cross-reactivity between dalbavancin and vancomycin. Side effects
The most common adverse reactions encountered in Phase II and Phase III trials were nausea (5.5%), headache (4.7%), and diarrhea (4.4%), as well as rash (2.7%) and itchiness (2.1%). Other less frequent but serious adverse reactions included hematologic disorders, hepatotoxicity, Clostridium difficile colitis, bronchospasm, infusion-related reactions including Red Man Syndrome, and anaphylactic shock. In trials, dalbavancin was associated with higher rates of hemorrhagic events compared to comparator groups and should be a precaution in patients undergoing surgery or taking anticoagulants.