AJVR, Vol 73, No. 10, October 2012 1641 M edications administered in water have been used extensively in the livestock industries to treat pop- ulations of animals, yet few pharmacokinetic studies 1–3 have been conducted on medications administered in water. This is likely related to concerns with individual variability and the inability to adequately model phar- macokinetics of drugs for a population of animals with Evaluation of factors important in modeling plasma concentrations of tetracycline hydrochloride administered in water in swine Sharon E. Mason, DVM, PhD; Glen W. Almond, DVM, PhD; Jim E. Riviere, DVM, PhD; Ronald E. Baynes, DVM, PhD Objective—To model the plasma tetracycline concentrations in swine (Sus scrofa domesti- ca) treated with medication administered in water and determine the factors that contribute to the most accurate predictions of measured plasma drug concentrations. Sample—Plasma tetracycline concentrations measured in blood samples from 3 popula- tions of swine. Procedures—Data from previous studies provided plasma tetracycline concentrations that were measured in blood samples collected from 1 swine population at 0, 4, 8, 12, 24, 32, 48, 56, 72, 80, 96, and 104 hours and from 2 swine populations at 0, 12, 24, 48, and 72 hours hours during administration of tetracycline hydrochloride dissolved in water. A 1-com- partment pharmacostatistical model was used to analyze 5 potential covariate schemes and determine factors most important in predicting the plasma concentrations of tetracycline in swine. Results—2 models most accurately predicted the tetracycline plasma concentrations in the 3 populations of swine. Factors of importance were body weight or age of pig, ambient temperature, concentration of tetracycline in water, and water use per unit of time. Conclusions and Clinical Relevance—The factors found to be of importance, combined with knowledge of the individual pharmacokinetic and chemical properties of medications currently approved for administration in water, may be useful in more prudent adminis- tration of approved medications administered to swine. Factors found to be important in pharmacostatistical models may allow prediction of plasma concentrations of tetracycline or other commonly used medications administered in water. The ability to predict in vivo concentrations of medication in a population of food animals can be combined with bac- terial minimum inhibitory concentrations to decrease the risk of developing antimicrobial resistance. (Am J Vet Res 2012;73:1641–1649) traditional techniques. 4 One potential technique that could provide insight and improved pharmacokinetic modeling is population-based modeling with nonlin- ear mixed effects. 5 Few population pharmacokinetic studies 6–10 have been performed in veterinary medicine and none on medications administered via water. Only 1 study 6 has investigated the population pharmacoki- netics of doxycycline coadministered with paracetamol Received June 3, 2011. Accepted November 3, 2011. From the Department of Comparative Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606. Dr. Mason’s present address is Department of Biological Sciences, College of Arts and Sciences, Campbell University, Buies Creek, NC 27506. Dr. Riviere’s present address is College of Vet- erinary Medicine, Kansas State University, Manhattan, KS 66506. This manuscript represents a portion of a dissertation submitted by the first author to the North Carolina State University Department of Comparative Biomedical Sciences as partial fulfillment of the re- quirements for a Doctor of Philosophy degree. Supported by the Food Animal Residue Avoidance Databank and Pfizer Animal Health. Address correspondence to Dr. Mason (masons@campbell.edu). ABBREVIATIONS AIC Akaike information criterion BIC Bayesian information criterion CV Coefficient of variation F Bioavailability FOCE First-order conditional estimate Ke Elimination constant Kel Elimination rate constant LL Log likelihood value MIC Minimum inhibitory concentration Vd Volume of distribution Unauthenticated | Downloaded 03/17/23 02:15 PM UTC