PHARMACOKINETIC AND GALACTOPOIETIC RESPONSE TO RECOMBINANT VARIANTS OF BOVINE GROWTH-HORMONE

Two studies were designed to examine the pharmacokinetic and galactopo ietic potency of three molecular variants of recombinant-derived bovin e GH (rbGH): [Met(1), Leu(127)]-bGH, [Ala(1), Val(127)]-bGH and [Ala(1 ), Val(127), His(133)]-bGH. Histidine substitution for arginine at res idue 133 of rbGH was shown to impart thrombin resistance. In a Latin s quare design, nine lactating Holstein cows received a 25 mg rbGH bolus infusion via the jugular vein followed by frequent blood sampling ove r the next 12 h. The serum GH concentration data were found to fit to a two-compartment open model. Neither primary nor secondary kinetic pa rameter estimates differed significantly (P>0.05) among the three rbGH variants. Thus, the disposition of GH concentration at time t was des cribed by the equation C(t)=(1295.5 mu g/l) (e(-(0.11/min)(t))) + 317. 3 mu g/l)(e(-(0.03/min)(t))). Overall averages were: area under the cu rve=27.1 mg min per 1, 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 sec ond 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 we re increased by approximately 3-6 mu g/l, 5-15 mu g/l and 40-90 mu g d ay per 1 respectively. Ala(1), Val(127) rbGH treatments elicited great er blood GH concentrations than [Met(1), Leu(127)]-bGH when administer ed in an oil-based formulation. Blood GH responses did not directly tr anslate into milk response differences, possibly due to differences in biopotency or receptor availability. Thrombin resistance resulting fr om substitution of histidine at position 127 of rbGH did not affect bl ood GH pharmacokinetic parameters or milk response over other rbGH var iants.