Kwang-Hee Shin (1), Kyung-Sang Yu (2), Howard Lee (2), Jae-Yong Chung (2) and In-Jin Jang (2)
(1) College of Pharmacy, Research Institute of Pharmaceutical Science, Kyungpook National University, Deagu, Korea, (2) Department of Clinical Pharmacology & Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea
Objectives: A pegylated recombinant human granulocyte colony stimulating factor (G-CSF) has been used for treatment of neutropenia in cancer therapy. The study aimed to develop a pharmacokinetic/pharmacodynamics (PK/PD) model of a pegylated G-CSF in healthy Korean to explore the relationship between plasma drug concentration and drug effect, absolute neutrophil count (ANC).
Methods: A dose-block randomized, double-blind, single-dose study was performed. Twenty five volunteers were randomly received a single subcutaneous (SC) pegylated G-CSF injection at a dose of 30 (n=10), 100 (n=10), or 300 (n=5) μg/kg or placebo in a 4:1 ratio. Plasma concentrations (PK) and ANC (PD) data were obtained up to 14 days after study drug administration. The data were fitted to a PK/PD model using non-linear mixed-effects modelling implemented in NONMEM V7.2.0 [1].
Results: Sequential PK/PD model was developed and the first-order conditional estimation with interaction in NONMEM was employed for model run. A one-compartment model with first-order absorption and first-order elimination described the PK. Stimulatory Emax model was well fitted for ANC profiles.
Conclusions: The time-profiles of the concentration and ANC in healthy Korean were well described by the developed model. Further PK-PD modeling with patient data may be useful tool to provide clinically relevant dosage regimen in neutropenia patients.
References:
[1] Beal SL, Sheiner LB, Boeckmann AJ & Bauer RJ (Eds.) NONMEM Users Guides. 1989-2011. Icon Development Solutions, Ellicott City, Maryland, USA.
Reference: PAGE 23 () Abstr 3266 [www.page-meeting.org/?abstract=3266]
Poster: Drug/Disease modeling - Oncology