Plasma concentration, mammary excretion and side‐effects of phenylbutazone after repeated oral administration in healthy cows

Abstract

Seven clinically healthy dairy cows were each given 2.5 g phenylbutazone (approximately 5 mg/kg body weight) by oral administration twice daily for 8 days. The concentrations of phenylbutazone in plasma and milk and several blood parameters were studied. The minimum plasma concentration during steady state was 100.4 +/- 7.3 micrograms/ml. During the same period the milk concentration never exceeded 1% of the plasma concentration. The elimination half-life in plasma was 38.6 +/- 3.7 h. Five days after administration had been discontinued, the milk concentration was 0.05 +/- 0.01 microgram/ml. All seven cows were clinically healthy throughout the experiment. The most pronounced side-effect of the blood parameters studied was a decreased concentration of leucocytes to about two-thirds of the control value. This might have a pronounced influence on the effectiveness of the immune system. There was also a significant decrease in total bilirubin indicating a decrease in the breakdown of erythrocytes.

Pharmacokinetics of phenylbutazone in beef steers

“…The two most common metabolites of phenylbutazone, oxyphenbutazone and hydroxphenylbutazone, were not present in any significant amounts (data not shown). This supports previous reports that demonstrate that this drug undergoes relatively limited and slow biotransformation in cattle (Martin et al ., 1984; Lees et al ., 1988). Phenylbutazone pharmacokinetic parameters as determined from plasma are presented in Table 1.…”

“…Phenylbutazone undergoes only limited metabolism in cattle regardless of sex, age and presence or absence of lactation (Martin et al ., 1984; Lee et al ., 1988; Williams et al ., 1990; Semrad et al ., 1993; De Veau et al ., 1998). Furthermore, the drug is highly protein bound in the plasma of cattle (95–99.8%).…”

“…Furthermore, the drug is highly protein bound in the plasma of cattle (95–99.8%). Slightly different phenylbutazone plasma protein binding is reported among cows, neonatal calves and bulls, but these differences are small and may be attributed to the different means by which the amount of free drug has been determined (Martin et al ., 1984; Lee et al ., 1988; Williams et al ., 1990; Semrad et al ., 1993; De Veau et al ., 1998).…”

“…The phenylbutazone pharmacokinetic parameters of steers listed in Tables 1 and 2 for total drug in plasma, t 1/2 , volume of distribution at steady state ( V ss ), volume of distribution during the elimination phase ( V z ), total body clearance (Cl) and AUC are statistically similar to those previously reported for lactating dairy cows (Martin et al ., 1984; De Veau et al ., 1998) as well as nonlactating cows (Eberhardson et al ., 1979; Lee et al ., 1988). The relatively low mean V ss and V z (140 and 144 mL/kg, respectively) to total body water of cattle (570 mL/kg, Ruckenbusch et al ., 1991) reflects the high degree of drug plasma protein binding of phenylbutazone (Fig.…”

“…There is considerable evidence that phenylbutazone is used in an extra‐label manner in cattle for the treatment of certain types of mastitis in lactating cows (Dascanio et al ., 1995; Shpigel et al ., 1998), as an anti‐inflammatory and antipyretic in the treatment of bacterial infections in neonatal calves (Semrad et al ., 1993), and to treat various musculoskeletal disorders, including arthritis, in bulls (Williams et al ., 1990). The mean half‐life of phenylbutazone in dairy cows is about 40 h (Eberhardson et al ., 1979; Martin et al ., 1984; Lee et al ., 1988; De Veau et al ., 1998). Neonatal calves have a mean phenylbutazone half‐life of about 207 h (Semrad et al ., 1993), while mature bulls have a mean phenylbutazone half‐life of 62 h (Williams et al ., 1990).…”