Pharmacokinetics and galactopoietic response to recombinant variants of bovine growth hormone

P. J. Eppard, T. C. White, B. K. Birmingham, R. L. Hintz, L. A. Bentle, D. C. Wood, W. J. Salsgiver, E. Rowold, M. A. Miller, S. Ganguli, M. D. Hale, G. G. Krivi, Robert J Collier, G. M. Lanza

Research output: Contribution to journalArticle

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Abstract

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 to 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 μg/l) (e(-(0.11/min)(t))) + (317.3 μg/l)(e(-(0.03/min)(t))). Overall averages were: area under the curve = 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 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 μg/l, 5-15 μg/l and 40-90 μg · 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.

Original languageEnglish (US)
Pages (from-to)441-450
Number of pages10
JournalJournal of Endocrinology
Volume139
Issue number3
StatePublished - 1993
Externally publishedYes

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Pharmacokinetics
Histidine
Thrombin
Area Under Curve
Oils
Milk
bovine growth hormone
Jugular Veins
Serum
Arginine
Injections
Therapeutics

ASJC Scopus subject areas

  • Endocrinology

Cite this

Eppard, P. J., White, T. C., Birmingham, B. K., Hintz, R. L., Bentle, L. A., Wood, D. C., ... Lanza, G. M. (1993). Pharmacokinetics and galactopoietic response to recombinant variants of bovine growth hormone. Journal of Endocrinology, 139(3), 441-450.

Pharmacokinetics and galactopoietic response to recombinant variants of bovine growth hormone. / Eppard, P. J.; White, T. C.; Birmingham, B. K.; Hintz, R. L.; Bentle, L. A.; Wood, D. C.; Salsgiver, W. J.; Rowold, E.; Miller, M. A.; Ganguli, S.; Hale, M. D.; Krivi, G. G.; Collier, Robert J; Lanza, G. M.

In: Journal of Endocrinology, Vol. 139, No. 3, 1993, p. 441-450.

Research output: Contribution to journalArticle

Eppard, PJ, White, TC, Birmingham, BK, Hintz, RL, Bentle, LA, Wood, DC, Salsgiver, WJ, Rowold, E, Miller, MA, Ganguli, S, Hale, MD, Krivi, GG, Collier, RJ & Lanza, GM 1993, 'Pharmacokinetics and galactopoietic response to recombinant variants of bovine growth hormone', Journal of Endocrinology, vol. 139, no. 3, pp. 441-450.
Eppard PJ, White TC, Birmingham BK, Hintz RL, Bentle LA, Wood DC et al. Pharmacokinetics and galactopoietic response to recombinant variants of bovine growth hormone. Journal of Endocrinology. 1993;139(3):441-450.
Eppard, P. J. ; White, T. C. ; Birmingham, B. K. ; Hintz, R. L. ; Bentle, L. A. ; Wood, D. C. ; Salsgiver, W. J. ; Rowold, E. ; Miller, M. A. ; Ganguli, S. ; Hale, M. D. ; Krivi, G. G. ; Collier, Robert J ; Lanza, G. M. / Pharmacokinetics and galactopoietic response to recombinant variants of bovine growth hormone. In: Journal of Endocrinology. 1993 ; Vol. 139, No. 3. pp. 441-450.
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abstract = "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 to 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 μg/l) (e(-(0.11/min)(t))) + (317.3 μg/l)(e(-(0.03/min)(t))). Overall averages were: area under the curve = 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 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 μg/l, 5-15 μg/l and 40-90 μg · 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.",
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T1 - Pharmacokinetics and galactopoietic response to recombinant variants of bovine growth hormone

AU - Eppard, P. J.

AU - White, T. C.

AU - Birmingham, B. K.

AU - Hintz, R. L.

AU - Bentle, L. A.

AU - Wood, D. C.

AU - Salsgiver, W. J.

AU - Rowold, E.

AU - Miller, M. A.

AU - Ganguli, S.

AU - Hale, M. D.

AU - Krivi, G. G.

AU - Collier, Robert J

AU - Lanza, G. M.

PY - 1993

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N2 - 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 to 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 μg/l) (e(-(0.11/min)(t))) + (317.3 μg/l)(e(-(0.03/min)(t))). Overall averages were: area under the curve = 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 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 μg/l, 5-15 μg/l and 40-90 μg · 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.

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