Abstract
The aim of the research was an examination of potential impact of milk
yield on the intercompartmental clearance – distribution clearance as well
as determination of the variability of obtained pharmacokinetic parameters
by the population approach using a two-compartmental structural model.
Blood perfusion has a considerable impact on physiology of the udder and
kinetics of drugs that are distributed in this organ. The research was
performed on healthy Holstein- Friesian and Polish Black-White cows at the
age of 4-10 years. Determination of antibiotics (ampicillin, amoxicillin,
cefoperazone, penicillin G prokaine, cloxacillin, cefacetril)
concentration was carried out after their every intramammary
administration to one quarter of the udder. A population pharmacokinetic
model was created to fit milk concentration data. General milk yield of a
single cow was used as a variable. A population analysis was conducted
using non-linear mixed-effect modeling. The impact of milk productivity
was set solely by reference to intercompartmental clearance only in case
of penicillin G, cloxacillin and ampicillin. It, has been found that milk
yield, depending on a drug, influenced the distribution clearance of the
drug to varying degrees. It means indirectly that increased perfusion of
the udder has a different impact on drug distribution from the udder to
the bloodstream.
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