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

摘要

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±8years, body mass index 29.7±4.9kg/m2) received a continuous sc infusion of GH (3mg/24h) for 60h 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/0.5. h) vs. 4.6 (3.7-5.7. ng/ml/0.5. h); p 0.05], and reproducible results of diurnal GH variation were obtained during visit 2 [5.7 (4.6-7.4) ng/ml/0.5. h vs. 4.6 (3.8-6.0) ng/ml/0.5. h, 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.