Impact of moderate interval exercise versus supine rest on the pharmacokinetics and pharmacodynamic profiles of subcutaneously administered growth hormone in adult growth hormone deficient patients.

BACKGROUND

Diurnal variation in serum growth hormone (s-GH) levels after exogenous GH delivery has previously been reported in patients with no endogenous GH secretion. Changes in postural position or physical activity, leading to changes in blood flow and/or lymphatic drainage may be underlying explanations.

PRIMARY

OBJECTIVES

The primary aim of this study is to study a possible impact of exercise and supine rest on pharmacokinetics (PK) and day-to-day variation of subcutaneously (s.c.) administered GH in adult GH deficient (AGHD) patients.

SECONDARY

OBJECTIVE

The secondary aim of this study is to compare s-IGF-I, s-insulin, and plasma (p)-glucose profiles after a carbohydrate rich breakfast following s.c. GH injection vs. continuous infusion.

DESIGN AND

METHODS

During supine rest eight AGHD males (59.8±8 years, BMI 29.7±4.9 kg/m(2)) were treated with one daily s.c. GH injections of 3 mg/24 h for 48 h (treatment sessions A, B) or a continuous s.c. GH infusion of 3 mg/24 h for 60 h (treatment sessions C, D). Exercise comprised 1 h bicycling with 50 W load on two consecutive days during treatment sessions B and D.

RESULTS

Administration of GH as a bolus injection, but not as a continuous GH infusion, resulted in about 32% higher s-GH levels during exercise (60 min) as well as 30 min after (s-GH logAUC(B-A) difference was 0.28; 95% CI: 0.14-0.4; p<0.001). However, the total s-GH(AUC 0-24 h) (p=0.75) and s-IGF-I(AUC0-48 h) levels (p=0.51) remained unchanged between the two occasions. P-glucose and insulin profiles were significantly higher after carbohydrate rich breakfast before first and second dosing both following s.c. GH injection and continuous infusion (p<0.05).

CONCLUSIONS

Moderate exercise intermittently increased s-GH levels. These changes seem to have no clinical short-term relevance, since total s-GH(24 h) and s-IGF-I(48 h) levels were unaffected.