Original research (sidebar) September and October, 1998 Pharmacokinetic modeling of in-feed tetracyclines in pigs using a meta-analytic compartmental approach

Jerome R.E. del Castillo, DMV, IPSAV, MSc; Johanne Elsener, DMV; Guy P. Martineau, DMV, DESS

del Castillo JRE, Elsener J, Martineau GP. Pharmacokinetic modeling of in-feed tetracyclines in pigs using a meta-analytic compartmental approach. Swine Health Prod. 1998;6(5):189-202.

Complete article is here. Also available in PDF format (1.6MB)

Putting it into practice...

It is easy to calculate daily CTC and OTC feed dosages for metaphylaxis of swine respiratory diseases. Practitioners can predict plasma drug concentrations in pigs offered medicated feeds, according to daily feed intake and nycthemeral feeding behavior, and correlate this and the MIC for targeted bacteria to reduce the incidence or severity of clinical disease. These equations might be of special interest to practitioners in countries where antibiotic prescription is left to the practitioner's judgement.

Given the importance of the diurnal feeding behavior we observed in this study, we propose the following equations to calculate in-feed dosages of CTC and OTC dosages, from nursery to finishing phases:

(Equation 5)

(Equation 6)

Where:

• DCTC and DOTC are the dosage concentrations of OTC and CTC (in mg per kg BW) to be administered in feed to pigs in order to achieve the targeted plasma concentration TPL (in µg per mL).
• DFIR is daily feed intake of pigs, which is represented as a BW ratio (i.e., if the amount of feed daily ingested is equivalent to 4% of BW, then a value of 0.04 is given to DFIR).
• DDMR is the ratio of daily meals eaten during the day by the pigs (i.e., if pigs eat nine of their 12 daily meals during the day, then DDMR has a value of 0.75).

As shown by the equation coefficients, the CTC dosage level needed to achieve a given plasma target concentration is almost 50% of the OTC level. On the other hand, coefficients of DFIR and DDMR in the equation to determine CTC dosage concentrations are 55% of those in the equation for OTC. This difference in the ratio of coefficients is associated with the faster clearance of CTC, as shown by k (Table 4).

Hypothetical example

You find pathogenic Pasteurella multocida is increasing the severity of respiratory signs caused by porcine reproductive and respiratory syndrome virus (PRRSV) in the growing section of a finisher operation. Affected pigs are 40 kg when they start to show clinical signs. Daily feed intake is 4.5%. You expect pigs at this weight to eat 67.5% of their daily meals during daytime (Table 1). The MIC of both CTC and OTC for the targeted bacterium is 0.25 mg per mL.

You would solve Equation 6 to determine the in-feed dosage for OTC:

DOTC = 35.25 - 64.85 + 62.85

DOTC = 33.25 mg/kg BW/day

And the required feed dosage for this hypothetical situation will thus be:

DOTC (feed)= 33.25/0.045
DOTC (feed)= 739 ppm

In the United States, this dosage exceeds the approved prescription dosage and is therefore not legal. You would then consider the alternative use of CTC, using Equation 5:

DCTC = 17.25 - 36.61 + 35.35

DCTC = 15.99 mg/kg BW/day

And the required in-feed dosage for this hypothetical situation will thus be:

DCTC (feed) = 15.99/0.045

DCTC (feed) = 355 ppm

This prescription dosage is legal in the United States.

The approximate dosages of OTC and CTC needed to achieve some specific concentrations in plasma are listed in Table 5.