THE EFFECT OF AGE ON PHENYLBUTAZONE PHARMACOKINETICS, METABOLISM AND PLASMA-PROTEIN BINDING IN GOATS

Phenylbutazone (PBZ) was administered intravenously as a single dose (10 mg/kg) to adult male and 1-day-, 10-day-, 4-week- and 6 week-old male goats. The plasma concentration of PBZ and its major metabolites oxyphenbutazone (OPBZ) and gamma-hydroxyphenbutazone (gamma-OHPBZ) was measured over time. The elimination half-life (t1/2beta) of PBZ decreased from 120 h in the 1-day-old to 16 h in the adult goats. Although the volume of distribution (V(d)) did not change significantly during maturation, the total body clearance (Cl B) increased from 2 ml.h-1.kg-1 in 1-day-old to 13 ml.h-1.kg-1 in the adult goats; the increase was 2-fold in the first 10 days of life. Oxyphenbutazone was detectable in the plasma of adult and 6-week-old goats as early as 15 min after PBZ administration. Its peak concentration occurred at 1.5 h (1.6 mug/ml) in adults and at 6 h (0.95 mug/ml) and 12 h (0.36 mug/ml) in 6- and 4-week-old goats respectively. The highest plasma concentration of gamma-OHPBZ was achieved in 4-week-old followed by 6-week-old and adult animals.