Serum profiles and short-term metabolic effect of pituitary and authentic biosynthetic human growth hormone in man

Jørgensen, J. O. L.; Flyvbjerg, Allan; Dinesen, J.; Lund, Hans T.; Alberti, K. G. M. M.; Ørskov, Hans; Christiansen, J. S.

doi:10.1530/acta.0.1160381

Cited by 24 publications

(26 citation statements)

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“…1). This difference has been recorded in 3 out of 4 studies which specifically com pared the two routes [6,7,11,13]. Similar findings have been made in absorption studies of insulin, and the dif ference is most likely related to the higher intramuscular blood flow.…”

Section: Route Of Gh Administrationsupporting

confidence: 66%

“…GH profiles following intramuscular or subcutaneous injections of 2 IU GH (Norditropin®) in 10 GH-deficient children on two separate occasions [13]. A more rapid absorption from the intramuscular bed, with a maximal absorption time of 2-3 h, and a disappearance phase from the serum of 12-20 h, is evident, as opposed to subcutaneous injections which yield values of 4-6 and 20-24 h, respectively ( fig.…”

Section: Route Of Gh Administrationmentioning

confidence: 99%

“…injections of 2 IU GH to 10 GH-deficient patients on two separate occasions. Data are derived from Jor gensen et al [13].…”

Section: Route Of Gh Administrationmentioning

confidence: 99%

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Pharmacological Aspects of Growth Hormone Replacement Therapy: Route, Frequency and Timing of Administration

Jørgensen

Møller²,

Møller³

et al. 1990

Horm Res

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Two or three weekly, daytime intramuscular injections of GH has been the traditional treatment of GH deficiency since the first studies. A recent reevaluation of the feasibility of subcutaneous GH injections revealed no side-effects, but a very strong preference by the patients for the subcutaneous route, and also an increase in growth rate in studies where the patients received daily injections given in the evening. That could indicate that the route, frequency and timing of GH administration may be of clinical importance. Subcutaneous injections result in a slower absorption, a smaller peak value, and a prolonged serum disappearance phase compared to intramuscular injections. This extends the periods of elevated serum GH levels in the patient, which might be advantageous. On the other hand, a reduced bioavailability of GH by the subcutaneous route has also been reported. The frequency of subcutaneous injections correlates positively with growth rate in animal studies. This is commonly ascribed to a closer resemblance to the endogenous pulsatile pattern. However, frequent subcutaneous injections do not induce a pulsatile pattern, but a pattern which is intermediary between continuous and true pulsatile administration. In a short-term patient study, we observed that pulsatile and continuous intravenous administration of GH generated identical increases in serum insulin-like growth factor I, which suggests that both pulsatory and constant, small elevations in serum GH are important for its actions. Concerning the time of administration, evening GH injections yield a more physiological pattern, and it has been shown that evening GH administration induces increased nitrogen retention and is more successful in normalizing circadian patterns of pertinent hormones and metabolites. In conclusion, it is likely that the route, frequency and time of GH administration have clinical implications.

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Section: Route Of Gh Administrationsupporting

confidence: 66%

Section: Route Of Gh Administrationmentioning

confidence: 99%

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Pharmacological Aspects of Growth Hormone Replacement Therapy: Route, Frequency and Timing of Administration

Jørgensen

Møller²,

Møller³

et al. 1990

Horm Res

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“…kg¢ recommended subcutaneously in humans as a replacement therapy and has previously been shown in the same experimental model to cause coronary vasoconstriction (Vacca et al 1998). The plasma levels achieved by such doses were within those previously published in humans treated by growth hormone and when the secretion of growth hormone was stimulated (Jorgensen et al 1987;Blum, 1992;Lanes et al 1995). Recordings taken during the steady state before injection of growth hormone were used as control.…”

Section: Experimental Protocolmentioning

confidence: 74%

The Role of Nitric Oxide in the Coronary Vasoconstriction Caused by Growth Hormone in Anaesthetized Pigs

Molinari

Battaglia

Bona

et al. 2000

Experimental Physiology

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Intravenous injection of growth hormone in anaesthetized pigs has been shown to cause coronary vasoconstriction by antagonizing the vasodilatory effects of β2‐adrenergic receptors. Because nitric oxide is believed to modulate or mediate β2‐adrenergic effects, the present study was undertaken in the same experimental model to determine the role of nitric oxide in the above response to growth hormone. In fourteen pigs anaesthetized with sodium pentobarbitone, changes in left circumflex or anterior descending coronary blood flow caused by intravenous injection of 0.05 i.u. kg‐1 of growth hormone at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. In a first control group of six pigs, growth hormone caused a decrease in coronary blood flow which averaged 13.1% of the baseline values. In a second group of eight pigs, intravenous administration of Nω‐nitro‐L‐arginine methyl ester (L‐NAME) was used to block the endothelial release of nitric oxide. In these pigs, the subsequent injection of growth hormone did not cause any significant changes in coronary blood flow, even when performed after reversing the increase in arterial blood pressure and coronary vascular resistance caused by L‐NAME with continuous intravenous infusion of papaverine. These results indicated that the coronary vasoconstricting effect of growth hormone, known to involve antagonism of β2‐adrenergic vasodilatory effect, was mediated by inhibition of nitric oxide release.

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“…route of administration generally provides the greatest and most rapid peak serum level, and a delayed absorption from the s. [23]. For met-hGH.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Short-Term Metabolic Effects of Mammalian Cell-Derived Biosynthetic Human Growth Hormone in Man

Zeisel¹,

Petrykowski²,

Wais³

1992

Horm Res

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The pharmacokinetics and acute effects of an authentic recombinant DNA-derived human growth hormone (rhGH) produced by genetically engineered mammalian cells were determined in 12 healthy volunteers following intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) administration of 4IU (1.3 mg) hGH/m² body surface area. Following i.v. administration, apparent elimination half-life of rhGH was 18 min. Following i.m. administration, a mean peak serum concentration of 36.9 ng/ml (range 13-61 ng/ml) occurred at 3 h, and following s.c. administration, more sustained but lower serum concentrations occurred, with mean peak concentrations of 16.4 and 16.3 ng/ml at 4 and 6 h (ranges 9.0-27.5 ng/ml and 6.5-35.5 ng/ml at 4 and 6 h, respectively). The mean area under the curves was lower after s.c. (134 ± 48 ng·h·mH) than after i.m. (194 ± 48 ng·h·ml^-1) injections (p < 0.03). Comparable results were obtained for the same dose of rhGH given subcutaneously in concentrations of either 4 IU/ml or 10 IU/ml. Both i.m. and s.c. administrations caused similar increases in free fatty acids at 4 h and insulin-like growth factor I at 24 h. Insulin, C-peptide and blood glucose were almost unchanged during the first 4 h after administration, whereas leukocytes increased significantly (p < 0.0001). Local and systemic tolerance were good, and no adverse reactions were observed. In a GH-deficient child, hGH serum levels between 10 and 20 ng/ml were demonstrated for a period of 8 h after s.c. administration of 0.07 IU rhGH/kg body weight.

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Serum profiles and short-term metabolic effect of pituitary and authentic biosynthetic human growth hormone in man

Cited by 24 publications

References 0 publications

Pharmacological Aspects of Growth Hormone Replacement Therapy: Route, Frequency and Timing of Administration

Pharmacological Aspects of Growth Hormone Replacement Therapy: Route, Frequency and Timing of Administration

The Role of Nitric Oxide in the Coronary Vasoconstriction Caused by Growth Hormone in Anaesthetized Pigs

Pharmacokinetics and Short-Term Metabolic Effects of Mammalian Cell-Derived Biosynthetic Human Growth Hormone in Man

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