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 (t 1/2 beta) of PBZ decreased from 120 h in the 1-day-old to 16 h in the adult goats. Although the volume of distribution (Vd) 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 micrograms/ml) in adults and at 6 h (0.95 micrograms/ml) and 12 h (0.36 micrograms/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.
Eltom
S E
SE
Department of Pharmacology, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Guard
C L
CL
Schwark
W S
WS
D000375:Aging / Q000502:physiology*; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006041:Goats / Q000378:metabolism*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D010653:Phenylbutazone / Q000378:metabolism / Q000493:pharmacokinetics*; D011485:Protein Binding
D001798:Blood Proteins; D010653:Phenylbutazone