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@ARTICLE{Fux:163744,
      author       = {Fux, Daniela and Metzner, Moritz and Brandl, Johanna and
                      Feist, Melanie and Behrendt-Wippermann, Magdalena and von
                      Thaden, Anne and Baumgartner, Christine},
      title        = {{P}harmacokinetics of metamizole (dipyrone) as an add-on in
                      calves undergoing umbilical surgery.},
      journal      = {PLOS ONE},
      volume       = {17},
      number       = {3},
      issn         = {1932-6203},
      address      = {San Francisco, California, US},
      publisher    = {PLOS},
      reportid     = {DZNE-2022-00483},
      pages        = {e0265305},
      year         = {2022},
      abstract     = {This preliminary clinical investigation of the
                      pharmacokinetic behavior of the main metamizole (dipyrone)
                      metabolites 4-methylaminoantipyrine (4-MAA) and
                      4-aminoantipyrine (4-AA) in calves undergoing umbilical
                      surgery is part of an already published main study. A single
                      intravenous dose of metamizole was added to
                      ketamine/xylazine/isoflurane anesthesia. Eight Simmental
                      calves weighing 90 ± 10.8 kg and aged 47.6 ± 10.4 days
                      received 40 mg/kg metamizole intravenously 10 minutes prior
                      to general anesthesia. Blood samples were collected over 24
                      hours and analyzed for 4-MAA and 4-AA. Meloxicam was
                      additionally given twice: 2.5 hours pre- and 20.5 hours
                      postsurgically. The pharmacokinetic profile of 4-MAA was
                      best fitted to a two-compartment model and was characterized
                      by a fast distribution half-life and slow elimination
                      half-life (t½alpha = 5.29 minutes, t½beta = 9.49 hours).
                      The maximum concentration (Cmax 101.63 μg/mL) was detected
                      at the first measurement time point 15 minutes after
                      administration. In contrast, 4-AA showed fast, high and
                      biphasic plasma peak concentration behavior in five calves
                      (2.54-2.66 μg/mL after 15-30 minutes, and 2.10-2.14 μg/mL
                      after 2-3.5 hours) with a t½beta of 8.87 hours, indicating
                      a rapid distribution and subsequent redistribution from
                      well-perfused organs. Alternatively, three calves exhibited
                      a slower and lower monophasic plasma peak concentration
                      (1.66 μg/mL after 6.5 hours) with a t½beta of 6.23 hours,
                      indicating slow accumulation in the intravascular
                      compartment. The maximum concentration and area under the
                      plasma concentration curve (AUC) of 4-AA were lower than
                      those of 4-MAA. This metabolic behavior supports our already
                      published data on clinical monitoring and plasma cortisol
                      concentrations (PCCs). Compared to those of saline controls,
                      lower PCCs correspond to the t½alpha of 4-MAA. Data on Tmax
                      and t½beta also match these clinical observations. However,
                      further studies are required to assess the exact analgesic
                      mechanism and potency of the metamizole metabolites in
                      calves.},
      keywords     = {Ampyrone / Analgesics / Animals / Cattle / Dipyrone /
                      Ketamine / Xylazine},
      cin          = {Animal Facility (Mouse) München},
      ddc          = {610},
      cid          = {I:(DE-2719)1140012},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:35290991},
      pmc          = {pmc:PMC8923478},
      doi          = {10.1371/journal.pone.0265305},
      url          = {https://pub.dzne.de/record/163744},
}