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.

Circadian variation in the pharmacokinetics of steady state continuous subcutaneous infusion of growth hormone in adult growth hormone deficient patients.

BACKGROUND: Previous studies in growth hormone (GH)-deficient (GHD) patients have indicated a possible diurnal variation in the pharmacokinetics (PK) of GH after subcutaneous (sc) GH administration. Thus, higher GH levels were observed during the night with continuous sc infusion, and increased GH bioavailability was reported following daily sc injections in the evening compared to morning. OBJECTIVE: The aim was to study whether diurnal variability in the PK of sc administered exogenous GH can be reproduced under standard conditions for all study participants, e.g. supine rest. DESIGN AND METHODS: Eight male GHD patients (59.8 ± 8 years, body mass index 29.7 ± 4.9 kg/m(2)) received a continuous sc infusion of GH (3mg/24h) for 60 h on two different occasions. Diurnal variation in PK of GH was studied during steady state in the last 24h of the infusion period. RESULTS: Median GH levels were higher at night time (23:00 h-07:00 h) than during the day (10:00 h-18:00 h) for visit 1 [5.1 (4.5-7.2 ng/ml/0.5h) vs. 4.6 (3.7-5.7 ng/ml/0.5h); p<0.05], and reproducible results of diurnal GH variation were obtained during visit 2 [5.7 (4.6-7.4) ng/ml/0.5h vs. 4.6 (3.8-6.0) ng/ml/0.5h, p<0.05]. Reproducible results between days 1 and 2 were also obtained during 08:30 h-20:30 h and 20:30 h-08:30 h, respectively. CONCLUSIONS: Previous findings of higher nocturnal GH levels were confirmed during steady state continuous sc GH infusion under standard conditions. The underlying mechanisms, e.g. whether GH absorption, distribution or elimination is primarily affected need to be further elucidated.