A comparative study of the pharmacokinetics of intravenous and oral trimethoprim/sulfadiazine formulations in the horse.
Abstract: The biopharmaceutical properties of four fixed trimethoprim/sulfonamide combinations were investigated in the horse. Eight fasted horses were dosed at 1 week intervals in a sequentially designed study with one intravenous (i.v.) and three oral trimethoprim/sulfadiazine (TMP/SDZ) formulations (1, 2 and 3) administered at a dose of 5 mg/kg trimethoprim (TMP) and 25 mg/kg sulfadiazine (SDZ). Plasma concentrations of each compound were monitored for 48 h. Pharmacokinetic parameters (volume of distribution, bioavailability and total body clearance) for TMP and SDZ were calculated and compared. After oral administration plasma concentrations of TMP and SDZ increased rapidly. With all three paste formulations, TMP peak plasma concentrations were attained within 2 h. SDZ mean peak plasma concentrations were reached at 2.59 +/- 0.48 h for a commercial paste (1), and at 1.84 +/- 0.66 h and 1.95 +/- 0.61 h for the two self-made formulations (2 and 3). Mean peak plasma TMP concentrations (+/- SD) were 1.72 +/- 0.36 micrograms/ml, 1.42 +/- 0.37 micrograms/ml and 1.31 +/- 0.36 micrograms/ml, and mean peak plasma SDZ concentrations 12.11 +/- 4.55 micrograms/ml, 12.72 +/- 3.47 micrograms/ml and 15.45 +/- 4.74 micrograms/ml for preparations 1, 2 and 3. The bioavailability of TMP was 67.0 +/- 20.3%, 57.7 +/- 21.6% and 60.9 +/- 18.9% and of SDZ 57.6 +/- 14.8%, 59.3 +/- 19.5% and 65.9 +/- 5.8% for SDZ for 1, 2 and 3, respectively. Following i.v. administration TMP/SDZ plasma concentration ratios approached the optimal 1:20 ratio (+/- 10%) for about 5 h, but following the oral administrations this ratio was only achieved for a very short time-span.(ABSTRACT TRUNCATED AT 250 WORDS)
Publication Date: 1994-12-01 PubMed ID: 7707489DOI: 10.1111/j.1365-2885.1994.tb00275.xGoogle Scholar: Lookup
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- Comparative Study
- Journal Article
Summary
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This research article studies the pharmacokinetics (how drugs are absorbed, distributed, metabolized, and eliminated by the body) of four types of drug combinations of trimethoprim and sulfonamide used in horses. The study compared the effects of these combinations when administered orally and intravenously.
Research Methodology
- The researchers tested the biopharmaceutical properties (like how the drugs dissolve, disperse, and are absorbed in the body) of four combinations of trimethoprim and sulfonamide.
- They used eight horses for this study, every horse being fasted and given a one-week interval between drug doses.
- The drugs were given in three oral forms and one intravenous form, all containing the same dosage of 5mg/kg of trimethoprim and 25mg/kg of sulfadiazine.
- The researchers monitored the plasma concentrations of each compound for 48 hours post administration.
- The main pharmacokinetics parameters studied were the volume of distribution, bioavailability (the proportion of the drug that enters circulation and is able to have an active effect), and the total body clearance of both the drugs.
Results and Findings
- After oral consumption, the plasma concentrations of trimethoprim and sulfadiazine increased rapidly.
- All three oral paste formulations enabled peak plasma concentrations of trimethoprim within two hours.
- Sulfadiazine reached its peak concentration slightly later. For commercial paste 1, it took about 2.59 hours, while for the two self-made formulations (2 and 3), it was around 1.84-1.95 hours.
- The bioavailability of trimethoprim was approximately 58-67%, and of sulfadiazine, it was around 58-66% in different oral formulations.
- The ideal ratio of plasma concentrations of trimethoprim to sulfadiazine is 1:20. After intravenous administration, this ratio could be maintained for about 5 hours, but the oral administrations could only achieve this ratio for a very short time.
Conclusion
- This research provides valuable data about the pharmacokinetics of trimethoprim and sulfadiazine, when given together, in horses and can guide veterinarians on their usage.
- However, the study reveals that oral formulations may not maintain the optimal drug concentration ratio in the body for as long as the intravenous ones. Therefore, the choice of administration method may vary based on the specific treatment goals.
Cite This Article
APA
van Duijkeren E, Vulto AG, Sloet van Oldruitenborghoosterbaan MM, Mevius DJ, Kessels BG, Breukink HJ, van Miert AS.
(1994).
A comparative study of the pharmacokinetics of intravenous and oral trimethoprim/sulfadiazine formulations in the horse.
J Vet Pharmacol Ther, 17(6), 440-446.
https://doi.org/10.1111/j.1365-2885.1994.tb00275.x Publication
Researcher Affiliations
- Department of Large Animal Medicine and Nutrition, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
MeSH Terms
- Administration, Oral
- Animals
- Drug Combinations
- Horses / metabolism
- Injections, Intravenous
- Trimethoprim, Sulfamethoxazole Drug Combination / administration & dosage
- Trimethoprim, Sulfamethoxazole Drug Combination / blood
- Trimethoprim, Sulfamethoxazole Drug Combination / pharmacokinetics
Citations
This article has been cited 8 times.- Ekstrand C, Nostell K, Gehring R, Bondesson U, Bröjer J. The disposition of trimethoprim and sulfadiazine in neonatal foals after intravenous administration.. Vet Med Sci 2022 May;8(3):1065-1071.
- Manca S, Upadhyaya B, Mutai E, Desaulniers AT, Cederberg RA, White BR, Zempleni J. Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns.. Sci Rep 2018 Jul 27;8(1):11321.
- Sadaka C, Kanellos T, Guardabassi L, Boucher J, Watts JL. Evaluation of Veterinary-Specific Interpretive Criteria for Susceptibility Testing of Streptococcus equi Subspecies with Trimethoprim-Sulfamethoxazole and Trimethoprim-Sulfadiazine.. J Clin Microbiol 2017 Jan;55(1):326-330.
- Stahl J, Zessel K, Schulz J, Finke JH, Müller-Goymann CC, Kietzmann M. The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings.. BMC Vet Res 2016 Apr 1;12:68.
- Chung YS, Song JW, Kim DH, Shin S, Park YK, Yang SJ, Lim SK, Park KT, Park YH. Isolation and characterization of antimicrobial-resistant Escherichia coli from national horse racetracks and private horse-riding courses in Korea.. J Vet Sci 2016 Jun 30;17(2):199-206.
- Bertin FR, Squires JM, Kritchevsky JE, Taylor SD. Clinical findings and survival in 56 sick neonatal New World camelids.. J Vet Intern Med 2015 Jan;29(1):368-74.
- Batzias GC, Delis GA, Koutsoviti-Papadopoulou M. Bioavailability and pharmacokinetics of sulphadiazine, N4-acetylsulphadiazine and trimethoprim following intravenous and intramuscular administration of a sulphadiazine/trimethoprim combination in sheep.. Vet Res Commun 2005 Nov;29(8):699-712.
- Baert K, De Baere S, Croubels S, De Backer P. Pharmacokinetics and oral bioavailability of sulfadiazine and trimethoprim in broiler chickens.. Vet Res Commun 2003 May;27(4):301-9.
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