Open AccessPharmacokinetics of metamizole (dipyrone) as an add-on in calves undergoing umbilical surgery
Author(s) -
Daniela Fux,
Moritz Metzner,
Johanna Brandl,
Michele I. Feist,
Magdalena Behrendt-Wippermann,
Anne von Thaden,
Christine Baumgartner
Publication year - 2022
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0265305
Subject(s) - metamizole , pharmacokinetics , xylazine , cmax , medicine , anesthesia , half life , meloxicam , volume of distribution , ketamine , analgesic , pharmacology
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 (t ½alpha = 5.29 minutes, t ½beta = 9.49 hours). The maximum concentration (C max 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 t ½beta 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 t ½beta 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 t ½alpha of 4-MAA. Data on T max and t ½beta also match these clinical observations. However, further studies are required to assess the exact analgesic mechanism and potency of the metamizole metabolites in calves.