1. About
Plasma and intestinal concentrations of sulfadiazine-trimethoprim in pigs after (non)conventional oral and intramuscular treatment, within the context of antimicrobial resistance
Department of Pharmacology, Toxicology and Biochemistry
Faculty of Veterinary Medicine, Ghent University, Belgium
Pharm. Joren De Smet

2. Context Impact on GIT exposure? Dosage and administration route
Dosing discrepancies of antimicrobials are observed in the Belgian field1
Oral therapy: often under dosed
Intramuscular therapy: often over dosed
1.Callens, B., et al., Prophylactic and metaphylactic antimicrobial use in Belgian fattening pig herds. Prev Vet Med, (1): p

3. Experimental setup 36 pigs, 6 pigs/ group Uniform feeding strategy
Allows for assessment
Dosing discrepancy
Administration route
Five-day treatment period
Daily collection blood and manure
End: collection GIT contents

4. Results – Plasma 1.1. Plasma concentrations SULFADIAZINE (0-108h)
Group 1 – Oral bolus
25 mg SDZ/ kg BW
Group 2 – Oral bolus
12.5 mg SDZ/ kg BW
Group 3 – IM injection
12.5 mg SDZ/ kg BW
Group 4 – IM injection
25 mg SDZ/ kg BW
Group 5 – Feed
25 mg SDZ/ kg BW
Group 6 – Feed
12.5 mg SDZ/ kg BW

5. Results – Plasma 1.2. Plasma concentrations TRIMETHOPRIM (0-108h)
Group 1 – Oral bolus
5mg TRIM/ kg BW
Group 2 – Oral bolus
2.5 mg TRIM/ kg BW
Group 3 – IM injection
2.5 mg TRIM/ kg BW
Group 4 – IM injection
5 mg TRIM/ kg BW
Group 5 – Feed
5 mg TRIM/ kg BW
Group 6 – Feed
2.5 mg TRIM/ kg BW

6. Results – Plasma Conclusions
IM administration results in highest Cpmax values for SDZ and TRIM
Oral gavage same magnitude
Medicated feed: lower plasma concentrations
Dosing discrepancy = difference in systemic exposure
Indicating linear pharmacokinetics

7. Results – Intestinal content
2. Intestinal concentrations SDZ-TRIM
End of therapy after 5 consecutive days
Intestinal concentrations of SDZ-TRIM were measured
Duodenum
Jejunum
Ileum
Cecum
Colon
Rectum

8. Dosage of 30 mg SDZ-TRIM/ kg bodyweight
Sulfadiazine
Trimethoprim

9. Dosage of 15 mg SDZ-TRIM/ kg bodyweight
Sulfadiazine
Trimethoprim

10. Results intestinal content
Conclusions
High oral bioavailabilities for SDZ-TRIM
Extensive absorption from proximal segments
Sulfadiazine
Literature: mainly renal excretion for SDZ
Our study: high levels of SDZ in GIT segments (~ Cpmax)
Accumulation in distal segments
Mechanism of gastro-intestinal secretion after absorption
Next, accumulation SDZ distal segments due to ion-trapping
With pKa 6.5, partly ionized at gut pH
Selection pressure for microbiota in GIT due to high SDZ levels

11. Results intestinal content
Conclusions
Trimethoprim
TRIM decreases towards distal segments
Full resorption and no intestinal secretion is assumed
Less selection pressure for microbiota in GIT

12. Future perspectives Project “DOSERESIST” (contract RF 14/6287).
New insights intestinal concentrations of antimicrobials
By evaluating different treatment strategies
Assess impact of these concentrations on resistance selection
By use of E.coli as indicator bacteria
In vitro model mimicking porcine gut

13. Acknowledgements
Department of Pharmacology, Toxicology and Biochemistry
Prof. Dr. P. De Backer
Prof. Dr. S. Croubels
Prof. Dr. M. Devreese