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.
Highlights
Umbilical surgeries are very frequent in calves and are often performed under general anesthesia using ketamine/xylazine and isoflurane, accompanied by pre- and postsurgical nonsteroidal anti-inflammatory drug (NSAID) application [1, 2]
4-MAA disappeared from the plasma in accordance with a two-compartment model, with a distribution half-life (t1⁄2alpha) of 5.29 minutes and an elimination half-life (t1⁄2beta) of 9.49 hours
Preliminary metabolic behavior data showed that presurgical applied metamizole is rapidly transformed into the analgesic metabolites 4-MAA and 4-AA in calves subjected to umbilical surgery under general anesthesia with ketamine, xylazine and isoflurane
Summary
Umbilical surgeries are very frequent in calves and are often performed under general anesthesia using ketamine/xylazine and isoflurane, accompanied by pre- and postsurgical nonsteroidal anti-inflammatory drug (NSAID) application [1, 2]. Whether the drug protocol efficiently eliminates perioperative pain in calves undergoing umbilical surgery is unclear. The NMDA receptor antagonist ketamine is a short-acting analgesic but is less effective in the control of visceral pain [4, 5]. A sufficient reduction of surgery-related inflammatory pain by NSAIDs is unclear [2]. Adequate control of surgical pain is of high importance in addition to ethical issues, because the effective reduction of perioperative pain significantly influences surgical outcome and recovery [6]. In the sense of multimodal balanced analgesia, different substance classes should be combined to produce the best possible analgesia with the fewest possible side effects. The use of only approved substances for food-producing animals limits this choice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
