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
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Objective: To assess effect of pharmacokinetic differences betweenchlortetracycline (CTC) and oxytetracycline (OTC), the effect of day/nightvariations in ad libitum intake of medicated feeds on variation in plasmaand tissue concentrations of both drugs, and the influence on the overallefficacy of metaphylactic strategies for bacterial respiratory disease ingrowing pigs.
Methods: A multidosage pharmacokinetic model was created for feed-administeredCTC and OTC in pigs. Parameters obtained by meta-analysis of published pharmacokineticarticles and a computerized iteration procedure were used to find minimumCTC or OTC in-feed dosage to maintain a selected plasma drug concentrationin pigs incorporating feeding behavior variables.
Results: The model accounted for daily feed consumption, ad libitumfeeding behavior, time-kill activity of tetracyclines, and the span of theirpostantibiotic effect. The model successfully passed an external validationprocedure. The bioavailability (P=.0001), apparent volume of distribution(P=.001), and elimination constant rate (P=.03) differed betweenCTC and OTC. When identical in-feed dosages are consumed, plasma concentrationsof CTC were twice the concentrations of OTC. Ad libitum feeding behavior,which becomes increasingly diurnal as pigs grow from weaning to finishing,induced major daily variations in plasma concentrations of both drugs. Wedevised two equations that easily calculate any specific result generatedby the computerized iteration procedure for CTC and OTC.
Implications: The use of either equation will allow swine practitionersto create more precise CTC or OTC metaphylactic strategies from weaningto finishing. Matching daily antibiotic dosages to what is needed can improvethe efficacy of metaphylaxis.