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A population pharmacokinetic (PK) analysis of ABX‐IL8, a fully human monoclononal IGG 2 antibody, in psoriasis patients
Author(s) -
Wang B.,
Roskos L.,
Osborn K.,
Lu H.,
Kim M.,
Pasumarthi R.,
Raie N.,
Tabrizi M.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.240
Subject(s) - abx test , medicine , interleukin 8 , population , pharmacokinetics , dosing , psoriasis , antibody , nonmem , pharmacology , immunology , inflammation , statistics , mathematics , environmental health
Background/Aims ABX‐IL8 is a fully human IgG 2 monoclonal antibody generated using transgenic XenoMouse® technology that binds to human interleukin‐8 with high affinity and specificity, and has been evaluated in various inflammatory diseases. The objective of this investigation was to develop a population PK model for ABX‐IL8 in psoriasis patients. Methods In this analysis, 878 PK observations from 81 psoriasis patients were pooled from 2 clinical trials and analyzed simultaneously using NONMEM. One study was a single‐dose, cohort dose‐escalation study with intensive PK sampling. The other was a multiple‐dose study in which ABX‐IL8 was administered intravenously once every 3 weeks for 12 weeks with sparse PK sampling. Weight‐adjusted dosing was used in both studies. Results The PK of ABX‐IL8 was adequately described by a 2‐compartment model with first‐order elimination. The estimated population mean (±SE) clearance (CL) was 0.260±0.010 L/d with an interindividual variability (IIV) of 28% CV. The estimated central (Vc) and peripheral (Vp) volumes of distribution were 4.14±0.14 L (IIV 24%) and 1.68±0.22 L (IIV 20%), respectively. From the covariate analysis, sex and age had no impact on the PK of ABX‐IL8. Body weight was a minor contributor to PK variability. Conclusions The PK of ABX‐IL8 in psoriasis patients was consistent with that of endogenous IgG antibodies, and was adequately described by the developed population model. Simulations support fixed dosing of ABX‐IL8. Clinical Pharmacology & Therapeutics (2005) 77 , P91–P91; doi: 10.1016/j.clpt.2004.12.240