title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. Electronic address: jurgita.janukonyte@clin.au.dk.
authors.forename: J
authors.initials: J
authors.lastname: Janukonytė
authors.affiliation: Department of Clinical Biochemistry, Horsens County Hospital, Aarhus, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Parkner
authors.affiliation: Department of Public Health, Section of General Practice, University of Aarhus, Aarhus, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Lauritzen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: J S
authors.initials: JS
authors.lastname: Christiansen
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University, Aarhus, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Frystyk
authors.affiliation: Research Unit for General Practice, University of Aarhus, Aarhus, Denmark.
authors.forename: H S
authors.initials: HS
authors.lastname: Pedersen
authors.affiliation: Department of Biomedicine (Clinical Pharmacology), Aarhus University, Aarhus, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Laursen
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002940:Circadian Rhythm; D015444:Exercise / Q000502:physiology*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000097:blood / Q000172:deficiency / Q000493:pharmacokinetics*; D006801:Humans; D007018:Hypopituitarism / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D012146:Rest / Q000502:physiology*; D016683:Supine Position / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019382:Human Growth Hormone
keywords: Diurnal variation; Exogenous growth hormone; Pharmacodynamics; Pharmacokinetics