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000163744 041__ $$aEnglish
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000163744 1001_ $$aFux, Daniela$$b0
000163744 245__ $$aPharmacokinetics of metamizole (dipyrone) as an add-on in calves undergoing umbilical surgery.
000163744 260__ $$aSan Francisco, California, US$$bPLOS$$c2022
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000163744 520__ $$aThis 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.
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000163744 650_2 $$2MeSH$$aAmpyrone
000163744 650_2 $$2MeSH$$aAnalgesics
000163744 650_2 $$2MeSH$$aAnimals
000163744 650_2 $$2MeSH$$aCattle
000163744 650_2 $$2MeSH$$aDipyrone
000163744 650_2 $$2MeSH$$aKetamine
000163744 650_2 $$2MeSH$$aXylazine
000163744 7001_ $$00000-0003-0752-6059$$aMetzner, Moritz$$b1
000163744 7001_ $$aBrandl, Johanna$$b2
000163744 7001_ $$aFeist, Melanie$$b3
000163744 7001_ $$aBehrendt-Wippermann, Magdalena$$b4
000163744 7001_ $$0P:(DE-2719)9000925$$avon Thaden, Anne$$b5$$udzne
000163744 7001_ $$00000-0001-6133-5099$$aBaumgartner, Christine$$b6
000163744 773__ $$0PERI:(DE-600)2267670-3$$a10.1371/journal.pone.0265305$$gVol. 17, no. 3, p. e0265305 -$$n3$$pe0265305$$tPLOS ONE$$v17$$x1932-6203$$y2022
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