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| 001 | 163744 | ||
| 005 | 20230915090534.0 | ||
| 024 | 7 | _ | |a 10.1371/journal.pone.0265305 |2 doi |
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| 037 | _ | _ | |a DZNE-2022-00483 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Fux, Daniela |b 0 |
| 245 | _ | _ | |a Pharmacokinetics of metamizole (dipyrone) as an add-on in calves undergoing umbilical surgery. |
| 260 | _ | _ | |a San Francisco, California, US |c 2022 |b PLOS |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a 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. |
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| 650 | _ | 2 | |a Ampyrone |2 MeSH |
| 650 | _ | 2 | |a Analgesics |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Cattle |2 MeSH |
| 650 | _ | 2 | |a Dipyrone |2 MeSH |
| 650 | _ | 2 | |a Ketamine |2 MeSH |
| 650 | _ | 2 | |a Xylazine |2 MeSH |
| 700 | 1 | _ | |a Metzner, Moritz |0 0000-0003-0752-6059 |b 1 |
| 700 | 1 | _ | |a Brandl, Johanna |b 2 |
| 700 | 1 | _ | |a Feist, Melanie |b 3 |
| 700 | 1 | _ | |a Behrendt-Wippermann, Magdalena |b 4 |
| 700 | 1 | _ | |a von Thaden, Anne |0 P:(DE-2719)9000925 |b 5 |u dzne |
| 700 | 1 | _ | |a Baumgartner, Christine |0 0000-0001-6133-5099 |b 6 |
| 773 | _ | _ | |a 10.1371/journal.pone.0265305 |g Vol. 17, no. 3, p. e0265305 - |0 PERI:(DE-600)2267670-3 |n 3 |p e0265305 |t PLOS ONE |v 17 |y 2022 |x 1932-6203 |
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