The first generic launched in Europe in 2009, and patent challenges were mounted in the US which led to invalidation of a key Lilly patent on its method to make the drug. Generic companies started selling the drug in the US in 2010 when the patent on the chemical itself expired. Patent litigation in China made headlines there and was resolved in 2010. Society and culture
As of 2017, gemcitabine was marketed under many brand names worldwide: Abine, Accogem, Acytabin, Antoril, axigem, Bendacitabin, Biogem, Boligem, Celzar, Citegin, Cytigem, Cytogem, Daplax, DBL, Demozar, Dercin, Emcitab, Enekamub, Eriogem, Fotinex, Gebina, Gemalata, Gembin, Gembine, Gembio, Gemcel, Gemcetin, Gemcibine, Gemcikal, Gemcipen, Gemcired, Gemcirena, Gemcit, Gemcitabin, Gemcitabina, Gemcitabine, Gemcitabinum, Gemcitan, Gemedac, Gemflor, Gemful, Gemita, Gemko, Gemliquid, Gemmis, Gemnil, Gempower, Gemsol, Gemstad, Gemstada, Gemtabine, Gemtavis, Gemtaz, Gemtero, Gemtra, Gemtro, Gemvic, Gemxit, Gemzar, Gentabim, Genuten, Genvir, Geroam, Gestredos, Getanosan, Getmisi, Gezt, Gitrabin, Gramagen, Haxanit, Jemta, Kalbezar, Medigem, Meditabine, Nabigem, Nallian, Oncogem, Oncoril, Pamigeno, Ribozar, Santabin, Sitagem, Symtabin, Yu Jie, Ze Fei, and Zefei. Research
Because it is clinically valuable and is only useful when delivered intravenously, methods to reformulate it so that it can be given by mouth have been a subject of research.Research into pharmacogenomics and pharmacogenetics has been ongoing. As of 2014, it was not clear whether or not genetic tests could be useful in guiding dosing and which people respond best to gemcitabine. However, it appears that variation in the expression of proteins (SLC29A1, SLC29A2, SLC28A1, and SLC28A3) used for transport of gemcitabine into the cell lead to variations in its potency.
TTP is a blood disorder and can lead to microangipathic hemolytic anemia (MAHA), neurologic abnormalities, fever, and renal disease. Pharmacology
Gemcitabine is hydrophilic and must be transported into cells via molecular transporters for nucleosides (the most common transporters for gemcitabine are SLC29A1 SLC28A1, and SLC28A3). After entering the cell, gemcitabine is first modified by attaching a phosphate to it, and so it becomes gemcitabine monophosphate (dFdCMP). This is the rate-determining step that is catalyzed by the enzyme deoxycytidine kinase (DCK). Two more phosphates are added by other enzymes. After the attachment of the three phosphates gemcitabine is finally pharmacologically active as gemcitabine triphosphate (dFdCTP). After being thrice phosphorylated, gemcitabine can masquerade as deoxycytidine triphosphate and is incorporated into new DNA strands being synthesized as the cell replicates.When gemcitabine is incorporated into DNA it allows a native, or normal, nucleoside base to be added next to it. This leads to "masked chain termination" because gemcitabine is a "faulty" base, but due to its neighboring native nucleoside it eludes the cells normal repair system (base-excision repair). Thus, incorporation of gemcitabine into the cells DNA creates an irreparable error that leads to inhibition of further DNA synthesis, and thereby leading to cell death.The form of gemcitabine with two phosphates attached (dFdCDP) also has activity; it inhibits the enzyme ribonucleotide reductase (RNR), which is needed to create new DNA nucleotides. The lack of nucleotides drives the cell to uptake more of the components it needs to make nucleotides from outside the cell, which also increases uptake of gemcitabine.