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Pharmacokinetics of phenylbutazone in plasma and milk of lactating dairy cows.

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 (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.
AuthorsE J De Veau, W Pedersoli, R Cullison, J Baker
JournalJournal of veterinary pharmacology and therapeutics (J Vet Pharmacol Ther) Vol. 21 Issue 6 Pg. 437-43 (Dec 1998) ISSN: 0140-7783 [Print] England
PMID9885966 (Publication Type: Journal Article)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Phenylbutazone
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (blood, pharmacokinetics)
  • Area Under Curve
  • Cattle (blood, metabolism)
  • Female
  • Half-Life
  • Injections, Intravenous (veterinary)
  • Lactation (blood, metabolism)
  • Milk (metabolism)
  • Phenylbutazone (blood, pharmacokinetics)

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