Table 1.
Parameter | Definition | Distribution | Data used to derive distribution |
---|---|---|---|
Rate of CTC abiotic degradation in GI tract and other body parts per hour | Beta (0·54, 37·4) | [5, 23, 26, 28–29] | |
Fraction of CTC excreted in bile | Uniform (0·39, 0·64) | ±25% estimate [26] | |
Fraction of CTC adsorbed to the digesta in the lower 2/3 of small intestine | Uniform (0·69, 0·89) | [33–34] | |
Fraction of CTC adsorbed to the digesta in large intestine | Uniform (0·69, 0·89) | [33–34] | |
Fraction of CTC adsorbed by the microbiome in the lower 2/3 of small intestinea | – | Not separately included in model simulations | |
Fraction of CTC adsorbed by the microbiome in large intestinea | – | Not separately included in model simulations | |
Fractional digesta flowb through stomachs to small intestine per hour | Ac: 0·0715 B: 0·0588 |
[35–36] | |
Fractional digesta flow through the upper 1/3 of small intestine per hour | A: 0·3333 B: 0·3077 |
[35, 37] | |
Fractional digesta flow through the lower 2/3 of small intestine per hour | A: 0·1330 B: 0·1330 |
[35, 37] | |
Fractional digesta flow through large intestine per hour (to defecation) | A: 0·1330 B: 0·2222 |
[35] | |
Vrest_si | Volume of digesta in the lower 2/3 of small intestine, litre | Uniform (4, 23) | [38] |
Vli | Volume of digesta in large intestine, litre | Uniform (6, 22) | [38] |
The animals ingested CTC in equal portions during each 12 h of day time per day of the 5-day therapy. The animals consumed feed and water at similar intervals to the drug.
The values of the parameters relevant for the drug concentrations in the central circulation were kept constant in all simulations, and were as in (Cazer et al. [6]).
A single variable – fraction of CTC adsorbed to the digesta or microbiome – was included in the simulations.
Intestinal transit time of CTC was set as the average of the liquid and solid digesta phases.
Forage scenarios were diets: A – grain based, and B – long-form hay based.