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Posts tagged with "Pharmacokinetics"

  • Biological News

    Modifying Red Blood Cells As Carriers

    What’s the best carrier to take some sort of therapeutic agent into the bloodstream? That’s often a tricky question to work out in animal models or in the clinic – there are a lot of possibilities. But what about using red blood cells themselves? That idea has been in the works for a few years… Read More
  • Biological News

    Single-Cell Compound Measurements – Now In A Real Animal

    Last year I mentioned an interesting paper that managed to do single-cell pharmacokinetics on olaparib, a poly(ADP) ribose polymerase 1 (PARP1) inhibitor. A fluorescently-tagged version of the drug could be spotted moving into cells and even accumulating in the nucleus. The usual warnings apply: adding a fluorescent tag can disturb the various mole… Read More
  • Drug Assays

    A New Way to Study Hepatotoxicity

    Every medicinal chemist fears and respects the liver. That’s where our drugs go to die, or at least to be severely tested by that organ’s array of powerful metabolizing enzymes. Getting a read on a drug candidate’s hepatic stability is a crucial part of drug development, but there’s an ever bigger prize out there: predicting… Read More
  • Pharmacokinetics

    Dosing by Body Surface Area

    We were talking about allometry around here the other day, which prompts me to mention this paper. It used the reports of resveratrol dosing in animals, crudely extrapolated to humans, to argue that the body surface area normalization (BSA) method was a superior technique for dose estimation across species. Over the years, though, the BSA… Read More
  • Drug Development

    A New Book on Scaffold Hopping

    I’ve been sent a copy of Scaffold Hopping in Medicinal Chemistry, a new volume from Wiley, edited by Nathan Brown of the Institute of Cancer Research in London. There are eighteen chapters – five on identifying and characterizing scaffolds to start with, ten on various computational approaches to scaffold-hopping, and three case histori… Read More
  • In Silico

    A New Metabolism Predictor

    Drug metabolism is a perennial topic for us small-molecule people. Watching your lovingly optimized molecules go through the shredding-machine of the liver is an instructive experience, not least when you consider how hard it would be for you to do some of the chemistry that it does. (For reference and getting up to speed on… Read More
  • Cardiovascular Disease

    Nasty Odor as a Drug Side Effect

    If you read the publications on the GSK compound (darapladib) that just failed in Phase III, you may notice something odd. These mention “odor” as a side effect in the clinical trial subjects. Say what? If you look at the structure, there’s a para-fluorobenzyl thioether in there, and I’ve heard that this is apparently not… Read More
  • Drug Assays

    Unraveling An Off-Rate

    Medicinal chemists talk a lot more about residence time and off rate than they used to. It’s become clear that (at least in some cases) a key part of a drug’s action is its kinetic behavior, specifically how quickly it leaves its binding site. You’d think that this would correlate well with its potency, but… Read More
  • Business and Markets

    Sugammadex’s Problems: Is the Merck/Schering-Plough Deal the Worst?

    That didn’t take long. Just a few days after Roger Perlmutter at Merck had praised the team that developed Bridon (sugammadex), the FDA turned it down for the second time. The FDA seems to be worried about hypersensitivity reactions to the drug – that was the grounds on which they rejected it in 2008. Merck… Read More
  • Drug Assays

    Too Many Metrics

    Here’s a new paper from Michael Shultz of Novartis, who is trying to cut through the mass of metrics for new compounds. I cannot resist quoting his opening paragraph, but I do not have a spare two hours to add all the links: Approximately 15 years ago Lipinski et al. published their seminal work linking… Read More