FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / Front Vet Sci / Pharmacokinetics of acetaminophen after a single Oral admini...
Frontiers in veterinary science2023; 10; 1198940; doi: 10.3389/fvets.2023.1198940

Pharmacokinetics of acetaminophen after a single Oral administration of 20 or 40 mg/kg to 7-9 Day-old foals.

Abstract: Acetaminophen is utilized in human infants for pain management and fever. Neonatal foals might benefit from administration of acetaminophen but effective and safe dosage regimens for neonatal foals remains to be determined. Unassigned: The objective was to determine the plasma pharmacokinetics of acetaminophen following oral administration of a single dose of 20 mg/kg or 40 mg/kg to neonatal foals. A secondary objective was to evaluate any changes in hematology and biochemistry profiles. Unassigned: Randomized study. Unassigned: Eight clinically healthy 7-9-day old Quarter Horse foals (3 colts and 5 fillies) received a single oral dose of acetaminophen either 20 (n = 4) or 40 (n = 4) mg/kg. Hematology and biochemistry profiles were evaluated before and 7 days after drug administration. Blood samples were collected before and 8 times after acetaminophen administration for 48 h to quantify plasma acetaminophen concentrations. Plasma pharmacokinetic parameters were estimated using non- compartmental analysis. Unassigned: The median peak plasma concentrations (and range) occurred at 1.5 (0.5-2) hours, and 1.0 (1-2) hours for the 20 and 40 mg/kg doses. The maximum plasma concentration (and range) was 12 (7.9-17.4) μg/mL for the 20 mg/kg dose and 14 (11-18) μg/mL for 40 mg/kg dose. The median AUC0-∞ ranged from 46 to 100 and 79 to 160 h*-μg/mL for the 20 and 40 mg/kg dose, respectively. Hematology and biochemistry profiles remained within normal limits. Unassigned: Plasma disposition of acetaminophen after oral administration of 20 and 40 mg/kg to neonates is comparable to adult horses. However, safety and the optimal dosage regimen of acetaminophen for treating pain and or pyrexia in neonates in this age group remains to be determined.
Copyright © 2023 Gold, Grubb, Court and Villarino.
Get Full Text
Publication Date: 2023-07-06 PubMed ID: 37483288PubMed Central: PMC10359069DOI: 10.3389/fvets.2023.1198940Google 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.
LinkedInCopy
  • 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.

The study investigates the pharmacokinetics, the process by which a drug is absorbed, distributed, metabolized, and expelled by the body, of acetaminophen in neonatal foals after administering a single oral dose. The research also monitors any changes in the foals’ hematology and biochemistry profiles. The findings suggest that the plasma disposition of acetaminophen in neonates is comparable to adult horses, but the safety and optimal dosage for treating pain and/or fever in neonates still need to be determined.

Research Methodology

  • The study utilized eight clinically healthy Quarter Horse foals aged 7-9 days, which each received a single oral dose of either 20 mg/kg (four foals) or 40 mg/kg (four foals) of acetaminophen.
  • Hematology and biochemistry profiles were assessed before and seven days after administration of the drug, to monitor any significant changes that could indicate potential side-effects.
  • Blood samples were collected from the foals before and at eight timepoints after the administration of acetaminophen over a 48-hour period. The samples were used to measure plasma acetaminophen concentrations.
  • Non-compartmental analysis was employed to estimate plasma pharmacokinetic parameters.

Findings

  • Peak plasma concentrations of acetaminophen were observed at 1.5 hours for the 20 mg/kg dose and 1.0 hour for the 40 mg/kg dose.
  • The maximum plasma concentration was 12 micrograms/mL for the lower dose, and 14 micrograms/mL for the higher dose.
  • The median AUC0-∞ (an indication of the total exposure of the body to the drug) varied from 46 to 100 hour*μg/mL for the 20 mg/kg dose and from 79 to 160 hour*μg/mL for the 40 mg/kg dose.
  • All hematological and biochemical profiles remained within regular limits, indicating the absence of adverse systemic reactions to the drug.

Conclusions

  • The findings reveal that the disposal of acetaminophen in the plasma following oral administration in neonates is comparable to that in adult horses, suggesting that the drug is processed similarly across different age groups.
  • Despite these findings, the study stresses that more research is needed to determine the safety and optimal dosage regimen of acetaminophen for treating pain and/or fever in neonatal foals.

Cite This Article

APA
Gold JR, Grubb T, Court MH, Villarino NF. (2023). Pharmacokinetics of acetaminophen after a single Oral administration of 20 or 40 mg/kg to 7-9 Day-old foals. Front Vet Sci, 10, 1198940. https://doi.org/10.3389/fvets.2023.1198940

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 10
Pages: 1198940

Researcher Affiliations

Gold, Jenifer R
  • Wisconsin Equine Clinic and Hospital, Oconomowoc, WI, United States.
Grubb, Tamara
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, United States.
Court, Michael H
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, United States.
Villarino, Nicolas F
  • Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, United States.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

This article includes 42 references
  1. Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE. PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses.. Pharmacogenet Genomics 2015 Aug;25(8):416-26.
    doi: 10.1097/FPC.0000000000000150pmc: PMC4498995pubmed: 26049587google scholar: lookup
  2. Graham GG, Davies MJ, Day RO, Mohamudally A, Scott KF. The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings.. Inflammopharmacology 2013 Jun;21(3):201-32.
    doi: 10.1007/s10787-013-0172-xpubmed: 23719833google scholar: lookup
  3. Elia N, Lysakowski C, Tramèr MR. Does multimodal analgesia with acetaminophen, nonsteroidal antiinflammatory drugs, or selective cyclooxygenase-2 inhibitors and patient-controlled analgesia morphine offer advantages over morphine alone? Meta-analyses of randomized trials.. Anesthesiology 2005 Dec;103(6):1296-304.
    doi: 10.1097/00000542-200512000-00025pubmed: 16306743google scholar: lookup
  4. Thybo KH, Hägi-Pedersen D, Dahl JB, Wetterslev J, Nersesjan M, Jakobsen JC, Pedersen NA, Overgaard S, Schrøder HM, Schmidt H, Bjørck JG, Skovmand K, Frederiksen R, Buus-Nielsen M, Sørensen CV, Kruuse LS, Lindholm P, Mathiesen O. Effect of Combination of Paracetamol (Acetaminophen) and Ibuprofen vs Either Alone on Patient-Controlled Morphine Consumption in the First 24 Hours After Total Hip Arthroplasty: The PANSAID Randomized Clinical Trial.. JAMA 2019 Feb 12;321(6):562-571.
    doi: 10.1001/jama.2018.22039pmc: PMC6439592pubmed: 30747964google scholar: lookup
  5. Prescott LF. Kinetics and metabolism of paracetamol and phenacetin.. Br J Clin Pharmacol 1980 Oct;10 Suppl 2(Suppl 2):291S-298S.
    doi: 10.1111/j.1365-2125.1980.tb01812.xpmc: PMC1430174pubmed: 7002186google scholar: lookup
  6. Mazaleuskaya LL, Sangkuhl K, Thorn CF, FitzGerald GA, Altman RB, Klein TE. PharmGKB summary: pathways of acetaminophen metabolism at the therapeutic versus toxic doses.. Pharmacogenet Genomics 2015 Aug;25(8):416-26.
    doi: 10.1097/FPC.0000000000000150pmc: PMC4498995pubmed: 26049587google scholar: lookup
  7. Court MH, Duan SX, von Moltke LL, Greenblatt DJ, Patten CJ, Miners JO, Mackenzie PI. Interindividual variability in acetaminophen glucuronidation by human liver microsomes: identification of relevant acetaminophen UDP-glucuronosyltransferase isoforms.. J Pharmacol Exp Ther 2001 Dec;299(3):998-1006.
    doi: 10.1046/j.1365-2125.2000.00231.xpubmed: 11714888google scholar: lookup
  8. Critchley JA, Nimmo GR, Gregson CA, Woolhouse NM, Prescott LF. Inter-subject and ethnic differences in paracetamol metabolism.. Br J Clin Pharmacol 1986 Dec;22(6):649-57.
    doi: 10.1111/j.1365-2125.1986.tb02953.xpmc: PMC1401198pubmed: 3567011google scholar: lookup
  9. Clements JA, Critchley JA, Prescott LF. The role of sulphate conjugation in the metabolism and disposition of oral and intravenous paracetamol in man.. Br J Clin Pharmacol 1984 Oct;18(4):481-5.
    doi: 10.1111/j.1365-2125.1984.tb02495.xpmc: PMC1463596pubmed: 6487489google scholar: lookup
  10. Sahajwalla CG, Ayres JW. Multiple-dose acetaminophen pharmacokinetics.. J Pharm Sci 1991 Sep;80(9):855-60.
    doi: 10.1002/jps.2600800911pubmed: 1800709google scholar: lookup
  11. Gelotte CK, Auiler JF, Lynch JM, Temple AR, Slattery JT. Disposition of acetaminophen at 4, 6, and 8 g/day for 3 days in healthy young adults.. Clin Pharmacol Ther 2007 Jun;81(6):840-8.
    doi: 10.1038/sj.clpt.6100121pubmed: 17377528google scholar: lookup
  12. Cook SF, Roberts JK, Samiee-Zafarghandy S, Stockmann C, King AD, Deutsch N, Williams EF, Allegaert K, Wilkins DG, Sherwin CM, van den Anker JN. Population Pharmacokinetics of Intravenous Paracetamol (Acetaminophen) in Preterm and Term Neonates: Model Development and External Evaluation.. Clin Pharmacokinet 2016 Jan;55(1):107-19.
    doi: 10.1007/s40262-015-0301-3pmc: PMC5564323pubmed: 26201306google scholar: lookup
  13. Cook SF, Stockmann C, Samiee-Zafarghandy S, King AD, Deutsch N, Williams EF, Wilkins DG, Sherwin CM, van den Anker JN. Neonatal Maturation of Paracetamol (Acetaminophen) Glucuronidation, Sulfation, and Oxidation Based on a Parent-Metabolite Population Pharmacokinetic Model.. Clin Pharmacokinet 2016 Nov;55(11):1395-1411.
    doi: 10.1007/s40262-016-0408-1pmc: PMC5572771pubmed: 27209292google scholar: lookup
  14. Wang C, Allegaert K, Tibboel D, Danhof M, van der Marel CD, Mathot RA, Knibbe CA. Population pharmacokinetics of paracetamol across the human age-range from (pre)term neonates, infants, children to adults.. J Clin Pharmacol 2014 Jun;54(6):619-29.
    doi: 10.1002/jcph.259pubmed: 24375166google scholar: lookup
  15. Anderson BJ, Woollard GA, Holford NH. A model for size and age changes in the pharmacokinetics of paracetamol in neonates, infants and children.. Br J Clin Pharmacol 2000 Aug;50(2):125-34.
    pmc: PMC2014402pubmed: 10930964doi: 10.1046/j.1365-2125.2000.00231.xgoogle scholar: lookup
  16. Arana A, Morton NS, Hansen TG. Treatment with paracetamol in infants.. Acta Anaesthesiol Scand 2001 Jan;45(1):20-9.
    doi: 10.1034/j.1399-6576.2001.450104.xpubmed: 11152028google scholar: lookup
  17. Doherty TJ, Andrews FM, Provenza MK, Frazier DL. Acetaminophen as a marker of gastric emptying in ponies.. Equine Vet J 1998 Jul;30(4):349-51.
    doi: 10.1111/j.2042-3306.1998.tb04109.xpubmed: 9705120google scholar: lookup
  18. Lohmann KL, Bahr A, Cohen ND, Boothe DM, Roussel AJ. Evaluation of acetaminophen absorption in horses with experimentally induced delayed gastric emptying.. Am J Vet Res 2002 Feb;63(2):170-4.
    doi: 10.2460/ajvr.2002.63.170pubmed: 11843113google scholar: lookup
  19. Neirinckx E, Vervaet C, De Boever S, Remon JP, Gommeren K, Daminet S, De Backer P, Croubels S. Species comparison of oral bioavailability, first-pass metabolism and pharmacokinetics of acetaminophen.. Res Vet Sci 2010 Aug;89(1):113-9.
    doi: 10.1016/j.rvsc.2010.02.002pubmed: 20211479google scholar: lookup
  20. Engelking LR, Blyden GT, Lofstedt J, Greenblatt DJ. Pharmacokinetics of antipyrine, acetaminophen and lidocaine in fed and fasted horses.. J Vet Pharmacol Ther 1987 Mar;10(1):73-82.
    doi: 10.1111/j.1365-2885.1987.tb00079.xpubmed: 3586126google scholar: lookup
  21. Fielding CL, Magdesian KG. Body water and fluid distribution in neonatal foals.. J Vet Emerg Crit Care (2009) 19:A11.
  22. Fischer B, Clark-Price S. Anesthesia of the Equine Neonate in Health and Disease.. Vet Clin North Am Equine Pract 2015 Dec;31(3):567-85.
    doi: 10.1016/j.cveq.2015.09.002pubmed: 26612748google scholar: lookup
  23. Bernard WV, Reimer JM. Examination of the foal.. Vet Clin North Am Equine Pract 1994 Apr;10(1):37-66.
    doi: 10.1016/S0749-0739(17)30368-1pubmed: 8039035google scholar: lookup
  24. Baggot JD, Short CR. Drug disposition in the neonatal animal, with particular reference to the foal.. Equine Vet J 1984 Jul;16(4):364-7.
    doi: 10.1111/j.2042-3306.1984.tb01945.xpubmed: 6479135google scholar: lookup
  25. Baggot JD. Drug therapy in the neonatal foal.. Vet Clin North Am Equine Pract 1994 Apr;10(1):87-107.
    doi: 10.1016/S0749-0739(17)30370-Xpubmed: 8039037google scholar: lookup
  26. Gold JR, Grubb T, Court M, Villarino NF. Pharmacokinetics of single dose administration of three increasing doses of acetaminophen per os in 1-3-month-old foals.. Equine Vet J 2023 Sep;55(5):891-898.
    doi: 10.1111/evj.13903pubmed: 36482786google scholar: lookup
  27. Mercer MA, McKenzie HC, Davis JL, Wilson KE, Hodgson DR, Cecere TE, McIntosh BJ. Pharmacokinetics and safety of repeated oral dosing of acetaminophen in adult horses.. Equine Vet J 2020 Jan;52(1):120-125.
    doi: 10.1111/evj.13112pubmed: 30900298google scholar: lookup
  28. Mercer MA, Davis JL, McKenzie HC, Byron CR, Kelleher ME, Trager L, Cecere TE, Wilson KE, Council-Troche RM, Werre SR. Pharmacokinetics, clinical efficacy and safety of acetaminophen (paracetamol) in adult horses with naturally occurring chronic lameness.. Equine Vet J 2023 Jun 7;.
    doi: 10.1111/evj.13601pubmed: 37287331google scholar: lookup
  29. Pesko B, Habershon-Butcher J, Muir T, Gray B, Taylor P, Fenwick S, Hincks P, Scarth J, Paine S. Pharmacokinetics of paracetamol in the Thoroughbred horse following an oral multi-dose administration.. J Vet Pharmacol Ther 2022 Jan;45(1):54-62.
    doi: 10.1111/jvp.13024pubmed: 34644412google scholar: lookup
  30. Yoon E, Babar A, Choudhary M, Kutner M, Pyrsopoulos N. Acetaminophen-Induced Hepatotoxicity: a Comprehensive Update.. J Clin Transl Hepatol 2016 Jun 28;4(2):131-42.
    doi: 10.14218/JCTH.2015.00052pmc: PMC4913076pubmed: 27350943google scholar: lookup
  31. Chun LJ, Tong MJ, Busuttil RW, Hiatt JR. Acetaminophen hepatotoxicity and acute liver failure.. J Clin Gastroenterol 2009 Apr;43(4):342-9.
    doi: 10.1097/MCG.0b013e31818a3854pubmed: 19169150google scholar: lookup
  32. https://digitalcommons.augustana.edu/cgi/viewcontent.cgi?article=1350&context=celebrationoflearning#:~:text=The%20slightly%20lower%20dosage%20(20,for%20up%20to%2030%20days.&text=There20are20no%20controlled%20studies%20of%20acetaminophen%20toxicity%20in%20horses.
  33. Foreman J, Foreman C, Bergstrom B. Acetaminophen/paracetamol efficacy in a reversible model of equine foot pain. In: AAEP annual convention, AAEP. Orlando, FL: AAEP; (2016). 295–6.
  34. Chinedu E, Arome D, Ameh FS. A new method for determining acute toxicity in animal models.. Toxicol Int 2013 Sep;20(3):224-6.
    doi: 10.4103/0971-6580.121674pmc: PMC3877490pubmed: 24403732google scholar: lookup
  35. Prior H, Haworth R, Labram B, Roberts R, Wolfreys A, Sewell F. Justification for species selection for pharmaceutical toxicity studies.. Toxicol Res (Camb) 2020 Dec;9(6):758-770.
    doi: 10.1093/toxres/tfaa081pmc: PMC7786171pubmed: 33442468google scholar: lookup
  36. Cook SF, King AD, van den Anker JN, Wilkins DG. Simultaneous quantification of acetaminophen and five acetaminophen metabolites in human plasma and urine by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry: Method validation and application to a neonatal pharmacokinetic study.. J Chromatogr B Analyt Technol Biomed Life Sci 2015 Dec 15;1007:30-42.
    doi: 10.1016/j.jchromb.2015.10.013pubmed: 26571452google scholar: lookup
  37. Gabrielsson J, Weiner D. Pharmacokinetic and pharmacodynamic data analysis: concepts and applications.. 4th ed Sweden: Swedish Pharmaceutical Press; (2007).
  38. Tan E, Braithwaite I, McKinlay CJD, Dalziel SR. Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.. JAMA Netw Open 2020 Oct 1;3(10):e2022398.
    pmc: PMC7599455pubmed: 33125495doi: 10.1001/jamanetworkopen.2020.22398google scholar: lookup
  39. Sarrell EM, Wielunsky E, Cohen HA. Antipyretic treatment in young children with fever: acetaminophen, ibuprofen, or both alternating in a randomized, double-blind study.. Arch Pediatr Adolesc Med 2006 Feb;160(2):197-202.
    doi: 10.1001/archpedi.160.2.197pubmed: 16461878google scholar: lookup
  40. Anderson B, Kanagasundarum S, Woollard G. Analgesic efficacy of paracetamol in children using tonsillectomy as a pain model.. Anaesth Intensive Care 1996 Dec;24(6):669-73.
    doi: 10.1177/0310057X9602400606pubmed: 8971314google scholar: lookup
  41. Bauer JE, Harvey JW, Asquith RL, McNulty PK, Kivipelto J. Clinical chemistry reference values of foals during the first year of life.. Equine Vet J 1984 Jul;16(4):361-3.
    doi: 10.1111/j.2042-3306.1984.tb01944.xpubmed: 6479134google scholar: lookup
  42. Harvey JW. Normal hematological values. In: Koterba AM, Drummond WH, Kosch PC, editors. Equine Clinical Neonatology. Philadelphia Lea and Febiger: (1990). 561–70.

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,021 horse owners like you who receive our email updates on horse health and nutrition.