Bioavailability and Pharmacokinetics of Sulphadiazine, N4-acetylsulphadiazine and Trimethoprim following Intravenous and Intramuscular Administration of a Sulphadiazine/Trimethoprim Combination in Sheep

  • G. C. Batzias
  • G. A. Delis
  • M. Koutsoviti-Papadopoulou
Article
Accepted:

Abstract

The combination of sulphadiazine and trimethoprim is extensively used in farm animal species; however, there are no data concerning its pharmacokinetics after intramuscular administration in sheep. Twelve rams of the Chios breed were used to study the disposition of sulphadiazine, its metabolite N4-acetylsulphadiazine and trimethoprim after intravenous (i.v.) and intramuscular (i.m.) administration of a sulphadiazine/trimethoprim (5:1) combination in sheep. Sulphadiazine bioavailability (±SD) was 69.00%±10.51%. The half-life of the terminal phase (4.10±0.58 h afteri. v., and 4.03±0.31 h after i.m. administration) was significantly higher than the respective value for trimethoprim (0.59±0.19 h) afteri.v. administration. The maintenance of a constant plasma concentration ratio after i.v. administration was therefore impossible. The acetylation capacity in sheep, determined by the AUC ratio between N4-acetylsulphadiazine and the parent compound, sulphadiazine, was very low (less than 4%). The most remarkable finding of this study was that trimethoprim was not detected in sheep plasma after i.m. injection. In conclusion, according to the findings of the present study, following i.v. administration of the sulphadiazine/trimethoprim combination, trimethoprim can be considered as the limiting factor for any possible synergistic effect, and the i.m. route cannot be recommended in sheep.

Keywords

bioavailability pharmacokinetics sheep sulphadiazine trimethoprim 

Abbreviations

AUC

area under the concentration–time curve

AUMC

area under the first moment curve

bw

body weight

Cl

total body clearance

Cmax

maximum plasma concentration

CV

coefficient of variation

F

bioavailability

HPLC

high-performance liquid chromatography

i.v.

intravenous(ly)

i.m.

intramuscular(ly)

LOQ

limit of quantification

MIC

mean inhibitory concentration

MRT

mean residence time

N4-acetyl-SDZ

N4-acetylsulphadiazine

NCA

non-compartmental analysis

p.o.

oral(ly)

SA

sulphonamides

s.c.

subcutaneous(ly)

SD

standard deviation

SDZ

sulphadiazine

SEM

standard error of the mean

SMX

sulphamethoxazole

t

terminal half-life

TBA

tetra-n-butylammonium hydrogensulphate

Tmax

time of maximum plasma concentration

TMP

trimethoprim

UV

ultraviolet

Vss

volume of distribution at steady state

Vz

volume of distribution based on the terminal (elimination) phase

lz

slope of the terminal portion of the concentration–time curve

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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • G. C. Batzias
    • 1
  • G. A. Delis
    • 1
  • M. Koutsoviti-Papadopoulou
    • 1
  1. 1.Laboratory of Veterinary Pharmacology, School of Veterinary MedicineAristotle University of Thessaloniki (A.U.Th.)ThessalonikiGreece

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