Modelling the concentration–time relationship in milk from cattle administered an intramammary drug

Abstract

Antimicrobial drugs are often infused directly through the streak canal into the bovine udder for the treatment or prevention of mastitis. These infusions have two major problems: drug residues in milk and variable antimicrobial efficacy. Both problems are influenced by the pharmacokinetics of intramammary delivery and elimination of drugs. This pharmacokinetics does not conform to the assumptions of traditional first-order mamillary pharmacokinetic models. To help understand drug delivery into and elimination from the udder, a new approach to pharmacokinetic modelling of the udder is proposed. This new model was used to predict the movement of drug within the udder and the concentrations of drug achieved within physiological compartments of the udder. These predictions were examined using computer modelling. The model was evaluated using data from in vivo intramammary infusion of cefuroxime. The model predicts that changes in milking efficiency (residual volume), milk productivity and milking frequency can impact both the drug residue persistence and the time that milk drug concentrations exceed the minimum inhibitory concentrations for pathogens. The model provides a new tool for future evaluation of intramammary dosing studies.

In vitro photoinactivation of bovine mastitis related pathogens

“…In the last few decades, there has been increased public concern related to the inspection of organs and the persistence of drug residues in milk products, which has motivated a series of studies currently under investigation [10][11][12]. In many countries, there was a reduction in the use of antimicrobial substances due to concern and public demand.…”

Viability of Mammary Bovine Leukocytes Challenged With Anti-Mastitis Drugs

“…Other authors that also investigated the effect of drugs on the mammary defense mechanisms (3,(10)(11)(12)(13) used different techniques and preparations. Dosogne et al (11) did not verify an interference with the in vitro phagocytic capacity of blood phagocytes exposed to preparations of cephapirin and mecylinamin, demonstrating that these drugs do not affect the viability of cells, which is similar to the results found in this study with the use of anhydrous cephalonium.…”

Pharmacokinetics and pharmacodynamics of a novel amoxicillin/sulbactam/prednisolone intramammary infusion in lactating cows after repeated administrations

“…According to Whitten et al and Stockler et al, milk composition and milk drug concentrations differed between fore-milk, pooled milk and milk strippings (Stockler et al 2009;Whitten et al 2012). In this study, fore-milk was collected from a single intramammary quarter to study the PK-PD of CAIMM in lactating cows.…”

“…would be helpful (Whitten et al 2012). Therefore, the compartmental and NCA model was studied to model the milk concentration-time data of SUL.…”

“…We found that milk SUL concentration-time data fit a single one compartment (data not shown). However, the single compartment that may be appropriate for consideration of drug residues does not assist in understanding efficacy because this model is simple and sampling data are limited (Whitten et al 2012). Considering the PK/PD integration of CAIMM and time-rich data with many collection time points, the NCA model was finally selected in this study.…”