1.The contribution of pharmacogenetics to pharmacovigilance.
Bondon-Guitton E1, Despas F2, Becquemont L3. Therapie. 2016 Mar-Apr;71(2):223-8. doi: 10.1016/j.therap.2016.02.005. Epub 2016 Mar 3.
Since the beginning of this century, information on pharmacogenetics appears in the summary of product characteristics (SPC) of drugs. Pharmacogenetic tests particularly concern the enzymes involved in the metabolism of drugs, among which P450 cytochromes. Some patients known as poor metabolisers eliminate some drugs more slowly, causing overdoses and adverse drug reactions (ADRs). The best-known examples are AVK and VKORC1-CYP2C9 or clopidogrel and CYP2C19. In the USA, the tests are recommended before the introduction of these drugs to prevent the occurrence of ADRs. Other tests are also commonly performed to address the toxicity of certain anticancer drugs (DPYD-capecitabine, UGT1A1-irinotecan, TPMT 6-mercaptopurine). Pharmacogenetic testing is also available to identify HLA loci that are very strongly associated with the occurrence of immuno-allergic reactions to a specific drug. The best-known example is HLA-B*5701, strongly associated with hypersensitivity to abacavir, and this test is now always prescribed before the instatement of this drug.
2.Time to Relapse in Children with Crohn's Disease Treated with Azathioprine and Nutritional Therapy or Corticosteroids.
Hradsky O1, Copova I2, Zarubova K2, Nevoral J2, Bronsky J2. Dig Dis Sci. 2016 Mar 12. [Epub ahead of print]
BACKGROUND: The duration of remission has been shown to be longer in patients initially treated with exclusive enteral nutrition (EEN) compared to corticosteroids (CS). However, no published studies required concurrent immunomodulator [6-mercaptopurine or azathioprine (AZA)] use at the time of diagnosis.
3.Improved pharmacokinetics of mercaptopurine afforded by a thermally robust hemihydrate.
Kersten KM1, Matzger AJ. Chem Commun (Camb). 2016 Apr 18;52(30):5281-4. doi: 10.1039/c6cc00424e. Epub 2016 Mar 22.
Structural and thermal data were obtained for a novel hemihydrate of 6-mercaptopurine. The hemihydrate shows increased solubility and bioavailability when compared to the monohydrate form, better stability against conversion in aqueous media than the anhydrate form, and a dehydration temperature of 240 °C, the highest of any known hydrate crystal.
4.6-Mercaptopurine attenuates tumor necrosis factor-α production in microglia through Nur77-mediated transrepression and PI3K/Akt/mTOR signaling-mediated translational regulation.
Huang HY1, Chang HF1, Tsai MJ2, Chen JS1, Wang MJ3. J Neuroinflammation. 2016 Apr 13;13(1):78. doi: 10.1186/s12974-016-0543-5.
BACKGROUND: The pathogenesis of several neurodegenerative diseases often involves the microglial activation and associated inflammatory processes. Activated microglia release pro-inflammatory factors that may be neurotoxic. 6-Mercaptopurine (6-MP) is a well-established immunosuppressive drug. Common understanding of their immunosuppressive properties is largely limited to peripheral immune cells. However, the effect of 6-MP in the central nervous system, especially in microglia in the context of neuroinflammation is, as yet, unclear. Tumor necrosis factor-α (TNF-α) is a key cytokine of the immune system that initiates and promotes neuroinflammation. The present study aimed to investigate the effect of 6-MP on TNF-α production by microglia to discern the molecular mechanisms of this modulation.