Comparative pharmacokinetics and pharmacodynamics of a new sustained-release growth hormone (GH), LB03002, versus daily GH in adults with GH deficiency

被引:47
作者
Bidlingmaier, Martin
Kim, John
Savoy, Conrad
Kim, Myung J.
Ebrecht, Nils
de la Motte, Stephan
Strasburger, Christian J.
机构
[1] Univ Munich, Med Klin Innenstadt, D-80336 Munich, Germany
[2] LG Lif Sci, Seoul 150721, South Korea
[3] BioPartners GmbH, CH-6340 Baar, Switzerland
[4] Harrison Clin Res, D-80636 Munich, Germany
[5] Charite Univ Med, D-10117 Berlin, Germany
关键词
D O I
10.1210/jc.2006-0514
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: 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. Design and Setting: This open-label, crossover study compared the pharmacokinetics and pharmacodynamics of LB03002 and daily GH. Patients and Other Participants: Six male and three female patients with adult GH deficiency participated in the single-center study. Intervention: 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. Main Outcome Measure: 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 mu g/liter at first and fifth doses) compared with daily GH (2.7 +/- 2.2 mu g/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.
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页码:2926 / 2930
页数:5
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