Pharmacokinetic Profiles of Metamizole Metabolites after Intramuscular and Intravenous Administration in Healthy Arabian Horses.
Abstract: Metamizole sodium (MT) is an analgesic and antipyretic drug molecule used in humans, horses, cattle, swine, and dogs. Metamizole rapidly hydrolyzes and turns into methylamino antipyrine (MAA), an active primary metabolite of MT. The present study aims to determine the pharmacokinetic (PK) profiles of MT metabolites after intravenous (IV) and intramuscular (IM) administration into sex of Arabian horses (Equus ferus caballus) using a cross-over study design. The plasma samples were extracted by solid-phase extraction (SPE) method, and plasma concentrations of MT metabolites were analyzed by high-performance liquid chromatography (HPLC). After administrations of MT, plasma concentrations of methylamino antipyrine (MAA), amino antipyrone (AA), and acetylamino antipyrone (AAA) were determined within range of 15 min-12 h. Plasma concentrations of AA and AAA were lower than the plasma concentrations of major metabolite MAA at each sampling point. The PK parameters were statistically evaluated for MT's metabolites between male and female horses and also between IM and IV administrations of PK parameters such as C , t , t , AUC , AUC , λz, Cl and V (p < .05). The AUC /AUC ratio in female and male horses for MAA was 1.19 and 1.13, respectively. The AUC /AUC ratio for AA was lower than those found for MAA. AUC /AUC ratio was statistically significantly different between male and female horses for AA (p < .05). According to these results, some PK parameters such as Cmax, AUC, and MRT, MAA and AA concentrations have shown statistically significant differences by MT administrations.
© 2021 John Wiley & Sons Ltd.
Publication Date: 2021-08-25 PubMed ID: 34431528DOI: 10.1111/jvp.13003Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This study investigates the breakdown and absorption of the drug Metamizole sodium (MT) in Arabian horses, observed through its metabolites. The work monitors concentrations of these substances in the animals’ blood over time, examining differences in uptake based on sex and method of drug delivery.
Research Methods
- The main research method utilized in the study involved the administration of Metamizole sodium to Arabian horses and then observing the amount of the primary metabolite, methylamino antipyrine (MAA), and two secondary metabolites, amino antipyrone (AA), and acetylamino antipyrone (AAA) in the horses’ blood plasma over a specified time range.
- These substances were detected and quantified using a high-performance liquid chromatography (HPLC) technique after extraction from the plasma samples via solid-phase extraction (SPE).
- The research design was cross-over in nature, meaning that the same horses were used to study the effects of the drug when both intramuscular (IM) and intravenous (IV) administration methods were employed.
Key Findings
- The researchers discovered that the concentration of the major metabolite MAA was consistently higher than the two secondary metabolites, AA and AAA, at all sampled points in the study. This suggests that MAA is the main substance resulting from the breakdown of Metamizole sodium in the horses’ bodies.
- The study also established statistical differences in the pharmacokinetic parameters for the metabolites based on administration methods and the sex of the horses involved.
- Important parameters such as peak concentration (C max), total exposure to the drug (AUC), and mean residence time (MRT) showed significant differences in intramuscular versus intravenous administration. Thus, the way the drug is administered could influence how it is broken down and absorbed in horses’ bodies.
- The AUC ratio, indicative of total drug exposure, was found to be different for MAA in male and female horses, suggesting that sex may influence the absorption and metabolization of Metamizole sodium in horses.
Concluding Remarks
- Through the findings of this study, researchers concluded that various factors, such as sex and administration method, can influence the breakdown and absorption of Metamizole sodium in horses.
- This determination has important implications for the therapeutic use of the drug in equine medicine and contributes to a more comprehensive understanding of drug pharmacokinetics in animals.
Cite This Article
APA
Yılmaz İ, Maraş Z, Uğur Y, Erkan Özgür M, Durmaz M, İbrahim Ulusoy H, Erdoğan S.
(2021).
Pharmacokinetic Profiles of Metamizole Metabolites after Intramuscular and Intravenous Administration in Healthy Arabian Horses.
J Vet Pharmacol Ther, 44(6), 927-936.
https://doi.org/10.1111/jvp.13003 Publication
Researcher Affiliations
- Department of Pharmacology, Faculty of Pharmacy, Inonu University, Malatya, Turkey.
- Department of Analytical Chemistry, Faculty of Pharmacy, Inonu University, Malatya, Turkey.
- Department of Pharmacy Services, Health Services Vocational School, Inonu University, Malatya, Turkey.
- Department of Aquaculture, Malatya Turgut Özal University, Doğanşehir Vahap Küçük Vocational High School, Malatya, Turkey.
- Ministry of Food, Agriculture and Animal Husbandry, Ankara, Turkey.
- Faculty of Pharmacy, Department of Analytical Chemistry, Cumhuriyet University, Sivas, Turkey.
- Department of Analytical Chemistry, Faculty of Pharmacy, Inonu University, Malatya, Turkey.
MeSH Terms
- Administration, Intravenous / veterinary
- Analgesics
- Animals
- Antipyrine / pharmacokinetics
- Area Under Curve
- Cross-Over Studies
- Dipyrone / pharmacokinetics
- Female
- Horses
- Male
Grant Funding
- This study was supported by Inonu University Scientific Research Fund (Project number: 2018/1044) for the financial support.
References
This article includes 36 references
- Aupanun S, Laus F, Poapolathep A, Owen H, Vullo C, Faillace V, Giorgi M. Pharmacokinetic Assessment of the Marker Active Metabolites 4-Methyl-amino-antipyrine and 4-Acetyl-amino-antipyrine After Intravenous and Intramuscular Injection of Metamizole (Dipyrone) in Healthy Donkeys. Journal of Equine Veterinary Science 47, 55-61.
- Baumgartner CM, Koenighaus H, Ebner JK, Henke J, Schuster T, Erhardt WD. Cardiovascular effects of dipyrone and propofol on hemodynamic function in rabbits. American Journal of Veterinary Research 70(11), 1407-1415.
- Castilhos TS, Barreto F, Meneghini L, Bergold AM. Development of high-throughput multi-residue method for non-steroidal anti-inflammatory drugs monitoring in swine muscle by LC-MS/MS. Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment 33(7), 1166-1174.
- Dirikolu L, Woods WE, Boyles J, Lehner AF, Harkins JD, Fisher M, Schaeffer DJ, Tobin T. Nonsteroidal anti-inflammatory agents and musculoskeletal injuries in Thoroughbred racehorses in Kentucky. Journal of Veterinary Pharmacology and Therapeutics 32(3), 271-279.
- Domínguez-Ramírez AM, Calzadilla PC, Cortés-Arroyo AR, Hurtado y de la Peña M, López JRM, Gómez-Hernández M, López-Muñoz FJ. High-performance liquid chromatographic assay for metamizole metabolites in rat plasma: Application to pharmacokinetic studies. Journal of Pharmaceutical and Biomedical Analysis 71, 173-178.
- Driessen B. Pain: Systemic and Local/Regional Drug Therapy. Clinical Techniques in Equine Practice 6(2), 135-144.
- Elmas M, Uney AK, Yazar E. Pharmacokinetics of flunixin-meglumin following intravenous administration in Angora rabbits. Bulletin of the Veterinary Institute in Pulawy 49(1), 85-88.
- Fiori M, Farn M, Civitareale C, Nasi A, Serpe L, Gallo P. The Use of Bovine Serum Albumin as a Ligand in Affinity Chromatographic Clean-up of Non-Steroidal Anti-Inflammatory Drugs from Bovine Plasma. Chromatographia 60(5-6), 253-257.
- Giorgi M, Aupanun S, Lee HK, Poapolathep A, Rychshanova R, Vullo C, Faillace V, Laus F. Pharmacokinetic profiles of the active metamizole metabolites in healthy horses. Journal of Veterinary Pharmacology and Therapeutics 40(2), 165-171.
- Giorgi M, De Vito V, Lee HK, Laus F, Kowalski C, Faillace V, Burmańczuk A, Vullo C. Pharmacokinetic investigations of the marker active metabolite-4-methylamino-antipyrin after intravenous and intramuscular injection of metamizole in healthy sheep. Small Ruminant Research 132, 143-146.
- Gyenge-Szabó Z, Szoboszlai N, Frigyes D, Záray G, Mihucz VG. Monitoring of four dipyrone metabolites in communal wastewater by solid phase extraction liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry. Journal of Pharmaceutical and Biomedical Analysis 90, 58-63.
- Hassan K, Khazim K, Hassan F, Hassan S. Acute kidney injury associated with metamizole sodium ingestion. Renal Failure 33(5), 544-547.
- Imagawa VH, Fantoni DT, Tatarunas AC, Mastrocinque S, Almeida TF, Ferreira F, Posso IP. The use of different doses of metamizol for post-operative analgesia in dogs. Veterinary Anaesthesia and Analgesia 38(4), 385-393.
- Jasiecka A, Maślanka T, Jaroszewski JJ. Pharmacological characteristics of metamizole. Polish Journal of Veterinary Sciences 17(1), 207-214.
- Jedziniak P, Pietruk K, Śledzińska E, Olejnik M, Szprengier-Juszkiewicz T, Żmudzki J. Rapid method for the determination of metamizole residues in bovine muscle by LC-MS/MS. Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment 30(6), 977-982.
- Jedziniak P, Szprengier-Juszkiewicz T, Olejnik M, Żmudzki J. Determination of non-steroidal anti-inflammatory drugs residues in animal muscles by liquid chromatography-tandem mass spectrometry. Analytica Chimica Acta 672(1-2), 85-92.
- Kamerling S, Wood T, DeQUICK D, Weckman TJ, Tai C, Blake JW, Tobin T. Narcotic analgesics, their detection and pain measurement in the horse: A review. Equine Veterinary Journal 21(1), 4-12.
- Klaus AM, Schlingloff Y, Kleinitz U, Böttcher M, Hapke HJ. Pharmacokinetic study of dipyrone metabolite 4-MAA in the horse and possible implications for doping control. Journal of Veterinary Pharmacology and Therapeutics 20(3), 204-208.
- Kobylińska K, Cendrowska I, Kobylińska M, Barlińska M. High-performance liquid chromatographic analysis for the determination of buspirone analogue - Mesmar in rat plasma. Acta Poloniae Pharmaceutica - Drug Research 57, 65-67.
- Kvaternick V, Pollmeier M, Fischer J, Hanson PD. Pharmacokinetics and metabolism of orally administered firocoxib, a novel second generation coxib, in horses. Journal of Veterinary Pharmacology and Therapeutics 30(3), 208-217.
- Letendre L, Kvaternick V, Tecle B, Fischer J. Automated liquid chromatography-tandem mass spectrometry method for the analysis of firocoxib in urine and plasma from horse and dog. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 853(1-2), 333-345.
- Lindegaard C, Ekstrøm CT, Wulf SB, Vendelbo JMB, Andersen PH. Nephrosplenic entrapment of the large colon in 142 horses (2000-2009): Analysis of factors associated with decision of treatment and short-term survival. Equine Veterinary Journal 43(39), 63-68.
- Maurer HH. Role of gas chromatography-mass spectrometry with negative ion chemical ionization in clinical and forensic toxicology, doping control, and biomonitoring. Therapeutic Drug Monitoring 24(2), 247-254.
- Mikami E, Goto T, Ohno T, Matsumoto H, Nishida M. Simultaneous analysis of naproxen, nabumetone and its major metabolite 6-methoxy-2-naphthylacetic acid in pharmaceuticals and human urine by high-performance liquid chromatography. Journal of Pharmaceutical and Biomedical Analysis 23, 917-925.
- Nikolova I, Petkova V, Tencheva J, Benbasat N, Voinikov J, Danchev N. Metamizole: A Review Profile of a Well-Known “Forgotten” Drug Part II: Clinical Profile, Biotechnology & Biotechnological Equipment (27-32). .
- Penney L, Bergeron C, Coates B, Wijewickreme A. Simultaneous Determination of Residues of Dipyrone and Its Major Metabolites in Milk, Bovine Muscle, and Porcine Muscle by Liquid Chromatography/Mass Spectrometry. Journal of AOAC International 88(2), 496-504.
- Ptáček P, Macek J, Klı́ma J. Rapid and simple high-performance liquid chromatographic determination of nimesulide in human plasma. Journal of Chromatography B: Biomedical Sciences and Applications 758, 183-188.
- Singh AK, Jang Y, Mishra U, Granley K. Simultaneous analysis of flunixin, naproxen, ethacrynic acid, indomethacin, phenylbutazone, mefenamic acid and thiosalicycic acid in plasma and urine by high-performance liquid chromatography and gas chromatography-mass spectrometry. Journal of Chromatography B: Biomedical Sciences and Applications 568(2), 351-361.
- Tanyildizi S, Bozkurt T. Effects of acetylsalicylic acid and metamizole on hyaluronidase activity and sperm characteristics in rams. Animal Reproduction Science 76(3-4), 195-204.
- Teixeira RCR, Monteiro ER, Campagnol D, Coelho K, Bressan TF, Monteiro BS. Effects of tramadol alone, in combination with meloxicam or dipyrone, on postoperative pain and the analgesic requirement in dogs undergoing unilateral mastectomy with or without ovariohysterectomy. Veterinary Anaesthesia and Analgesia 40(6), 641-649.
- Vlahov V, Badian M, Verho M, Bacracheva N. Pharmacokinetics of metamizole metabolites in healthy subjects after a single oral dose of metamizole sodium. European Journal of Clinical Pharmacology 38(1), 61-65.
- Yilmaz I, Elmas M. The bioequivalence determination of two different formulations of enrofloxacin in heifers following intramuscular administration. Kafkas Universitesi Veteriner Fakultesi Dergisi 16(3), 377-382.
- Zanuzzo FS, Teixeira-Neto FJ, Teixeira LR, Diniz MS, Souza VL, Thomazini CM, Steagall PVM. Analgesic and antihyperalgesic effects of dipyrone, meloxicam or a dipyrone-meloxicam combination in bitches undergoing ovariohysterectomy. The Veterinary Journal 205(1), 33-37.
- Zhang C, Zhang L, Cao S, Jiang Z, Wu H, Yan M, Zhang X, Jiang S, Xue F. Simultaneous determination of residues of dipyrone metabolites in goat tissues by hydrophilic interaction liquid chromatography tandem mass spectrometry. Food Chemistry 196, 83-89.
- Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, Xie S. DDSolver: An Add-In Program for Modeling and Comparison of Drug Dissolution Profiles. The AAPS Journal 12(3), 263-271.
- Zukowski M, Kotfis K. Safety of metamizole and paracetamol for acute pain treatment. Anestezjologia Intensywna Terapia 41(3), 170-175.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists