K. Saito,1 T. Mochizuki,1 A. Shimatsu,2 Y. Kasahara1; 1Teijin Pharma Limited, Tokyo, Japan, 2Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, Japan
BACKGROUND: The aim of this analysis was to develop a pharmacodynamic model evaluating the relationship between serum trough concentrations, growth hormone (GH) and insulin-like growth factor 1 (IGF-1) in Japanese acromegalic patients.
METHODS: In a dose-response study, 32 patients received 60, 90 or 120 mg of lanreotide autogel over 24 weeks. In a long-term study, 32 patients received 90 mg of lanreotide autogel starting dose during fixed-dose phase, followed by dose-titration phase. The data of both studies were included in this analysis. PD model for GH was compared between inhibitory Emax and inhibitory sigmoid Emax model. Emax model was used for PD model of IGF-1. The estimation was conducted using NONMEM 7 with FOCE-I. Covariates were tested by stepwise method, and included age, weight, gender, previous treatment (0 or 1), dose and week.
RESULTS: PD model for GH between serum trough concentration of lanreotide and GH was described by inhibitory sigmoid Emax model. The model showed significant decrease in objective function value. The final model was included inhibitory sigmoid Emax model for GH and Emax model for IGF-1, and PD parameters were estimated simultaneously. No covariate was selected in the model. The final model showed good performance with goodness-of-fit plots and visual predictive check. The estimated median serum trough concentration of lanreotide with GH control at ≤2.5 μg/L was 1.1 μg/L .
CONCLUSION: A population pharmacodynamic model was developed for lanreotide autogel in Japanese acromegalic patients. This model supports dosing and administration of lanreotide autogel in patients.