Comparative pharmacokinetics and pharmacodynamics of a new sustained-release growth hormone (GH), LB03002, versus daily GH in adults with GH deficiency.
BACKGROUND
LB03002 is a novel sustained-release GH preparation administered once weekly.


OBJECTIVE
Our objective was to examine the pharmacokinetics, pharmacodynamics, and safety of LB03002 vs. daily GH.


METHODS
This open-label, crossover study compared the pharmacokinetics and pharmacodynamics of LB03002 and daily GH.


METHODS
Six male and three female patients with adult GH deficiency participated in the single-center study.


METHODS
Subjects were on stable daily GH treatment before the study. After a 4-wk washout with no GH, five weekly doses of LB03002 were given.


METHODS
GH and IGF-I concentrations were measured during the last dose of daily GH and during the first and fifth weekly doses of LB03002.


RESULTS
The observed maximal serum GH concentration was approximately doubled after LB03002 (6.1 +/- 3.2 and 4.5 +/- 2.2 microg/liter at first and fifth doses) compared with daily GH (2.7 +/- 2.2 microg/liter). A sustained increase in GH concentration for more than 48 h was observed with LB03002, such that dose-normalized area under the curve (AUC) was not significantly different between daily GH and LB03002. Mean maximal serum IGF-I concentration was 34-41% greater with LB03002 than with daily GH, and AUC was 7-fold greater. However, normalized to GH dose, AUC for IGF-I was comparable. Adverse events and local reactions were acceptable, and there were no evident safety concerns with LB03002.


CONCLUSIONS
Multiple weekly doses of LB03002 appeared safe and well tolerated. Comparable GH bioavailability and sustained IGF-I elevations support the use of once-weekly LB03002 to replace daily GH therapy.
Bidlingmaier
Martin
M
Medizinische Klinik-Innenstadt, Ludwig-Maximilians-Universität, Ziemssenstrasse 1, 80336 Munich, Germany. martin.bidlingmaier@med.uni-muenchen.de
Kim
John
J
Savoy
Conrad
C
Kim
Myung J
MJ
Ebrecht
Nils
N
de la Motte
Stephan
S
Strasburger
Christian J
CJ
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D005215:Fasting; D005260:Female; D013006:Growth Hormone / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019382:Human Growth Hormone / Q000172:deficiency* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007700:Kinetics; D008297:Male; D008875:Middle Aged
D001786:Blood Glucose; D003692:Delayed-Action Preparations; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone