Pharmacokinetic and galactopoietic response to recombinant variants of bovine growth hormone.
Two studies were designed to examine the pharmacokinetic and galactopoietic potency of three molecular variants of recombinant-derived bovine GH (rbGH): [Met1, Leu127]-bGH, [Ala1, Val127]-bGH and [Ala1, Val127, His133]-bGH. Histidine substitution for arginine at residue 133 of rbGH was shown to impart thrombin resistance. In a Latin square design, nine lactating Holstein cows received a 25 mg rbGH bolus infusion via the jugular vein followed by frequent blood sampling over the next 12 h. The serum GH concentration data were found to fit a two-compartment open model. Neither primary nor secondary kinetic parameter estimates differed significantly (P > 0.05) among the three rbGH variants. Thus, the disposition of GH concentration at time t was described by the equation C(t) = (1295.5 micrograms/l) (e-(0.11/min)(t)) + (317.3 micrograms/l)(e-(0.03/min)(t)). Overall averages were: area under the curve = 27.1 mg.min per l, clearance = 0.15 litres/min per 100 kg and volume of distribution of the central compartment = 2.59 litres/100 kg. The t 1/2 for the two compartments averaged 8.2 and 29.1 min. In the second study, 36 lactating Holstein cows received i.m. injections of one of four oil-based formulation treatments: control vehicle or 500 mg of one of the three rbGH variants every 14 days for 42 days. Average and maximum serum GH concentrations and area under the curve estimates were increased by approximately 3-6 micrograms/l, 5-15 micrograms/l and 40-90 micrograms.day per 1 respectively. Ala1, Val127 rbGH treatments elicited greater blood GH concentrations than [Met1, Leu127]-bGH when administered in an oil-based formulation. Blood GH responses did not directly translate into milk response differences, possibly due to differences in biopotency or receptor availability. Thrombin resistance resulting from substitution of histidine at position 127 of rbGH did not affect blood GH pharmacokinetic parameters or milk response over other rbGH variants.
Eppard
P J
PJ
Agricultural Group, Monsanto Company, St. Louis, Missouri 63198.
White
T C
TC
Birmingham
B K
BK
Hintz
R L
RL
Bentle
L A
LA
Wood
D C
DC
Salsgiver
W J
WJ
Rowold
E
E
Miller
M A
MA
Ganguli
S
S
D000818:Animals; D002417:Cattle / Q000502:physiology*; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D006207:Half-Life; D007774:Lactation / Q000187:drug effects*; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology; D013917:Thrombin / Q000378:metabolism
D011994:Recombinant Proteins; D013006:Growth Hormone; D013917:Thrombin