Phenylbutazone was administered intravenously (i.v.) to a group of four lactating cows at a dosage of 6 mg/kg
body weight. Whole
plasma, protein-free plasma and milk were analysed for
phenylbutazone residues. Pharmacokinetic parameters of total and free
phenylbutazone in plasma were calculated using a non compartmental method. In regards to whole plasma data, the mean volume of distribution at steady state (Vss), was 147 mL/kg
body weight, with a mean (+/-SEM) terminal elimination half-life (t1/2) of 40+/-6 h. The mean clearance (Cl) was 3 mL/h/kg
body weight. The Vss as determined from the
protein-free plasma fraction was 50021 mL/kg
body weight. This larger Vss of free
phenylbutazone compared to total plasma
phenylbutazone was attributed to a high degree of
plasma protein binding, as well as the greater penetration of free
phenylbutazone into tissues. The mean t1/2 of free
phenylbutazone was 39+/-5 h. This similarity to the t1/2 estimated from total plasma
phenylbutazone data is attributed to an equilibrium between free and plasma
phenylbutazone during the terminal elimination phase. Mean t1/2 as determined from milk, applying a urinary excretion rate model, was 47+/-4 h. Milk clearance of
phenylbutazone was 0.009 mL/h/kg
body weight, or about 0.34% of total body clearance. Furthermore, evidence suggests that
phenylbutazone either binds to
milk proteins, or is actively transported into milk, as its concentration in milk was greater than that predicted due to a simple partitioning from plasma into milk.