Pharmacokinetics of phenylbutazone in plasma and milk of lactating dairy cows |
| |
| Authors: | De Veau Pedersoli Cullison & Baker |
| |
| Institution: | Division of Residue Chemistry, U.S. Food and Drug Administration (USFDA), Center for Veterinary Medicine (CVM), Office of Research (OR), 8401 Muirkirk Road, Laurel, Maryland 20708, USA.; Division of Animal Research, U.S. Food and Drug Administration (USFDA), Center for Veterinary Medicine (CVM), Office of Research (OR), 8401 Muirkirk Road, Laurel, Maryland 20708, USA.; Division of Animal Research, U.S. Food and Drug Administration (USFDA), Center for Veterinary Medicine (CVM), Office of Research (OR), 8401 Muirkirk Road, Laurel, Maryland 20708, USA.; USFDA/CVM/Office of New Animal Drug Evaluation, Division of Therapeutic Drugs for Non-Food Animals, 7500 Standish Place, Metro Park North II, Rockville, Maryland 20855, USA. |
| |
| Abstract: | 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 ( V ss), was 147 mL/kg body weight, with a mean (± SEM) terminal elimination half-life ( t 1/2) of 40 ± 6 h. The mean clearance ( Cl ) was 3 mL/h/kg body weight. The V ss as determined from the protein-free plasma fraction was 50 021 mL/kg body weight. This larger V ss 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 t 1/2 of free phenylbutazone was 39 ± 5 h. This similarity to the t 1/2 estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. Mean t 1/2 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. |
| |
| Keywords: | |
|
|
