TY  - JOUR
AU  - Fux, Daniela
AU  - Metzner, Moritz
AU  - Brandl, Johanna
AU  - Feist, Melanie
AU  - Behrendt-Wippermann, Magdalena
AU  - von Thaden, Anne
AU  - Baumgartner, Christine
TI  - Pharmacokinetics of metamizole (dipyrone) as an add-on in calves undergoing umbilical surgery.
JO  - PLOS ONE
VL  - 17
IS  - 3
SN  - 1932-6203
CY  - San Francisco, California, US
PB  - PLOS
M1  - DZNE-2022-00483
SP  - e0265305
PY  - 2022
AB  - 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.
KW  - Ampyrone
KW  - Analgesics
KW  - Animals
KW  - Cattle
KW  - Dipyrone
KW  - Ketamine
KW  - Xylazine
LB  - PUB:(DE-HGF)16
C6  - pmid:35290991
C2  - pmc:PMC8923478
DO  - DOI:10.1371/journal.pone.0265305
UR  - https://pub.dzne.de/record/163744
ER  -