C. Ambery (1), L. Aarons (1)
(1) School of Pharmacy and Pharmaceutical Sciences, University of Manchester, UK
Objectives: To develop a population pharmacokinetic model for ICL670 and the iron-complex Fe-[ICL670]2.
Methods: A population approach (implemented with NONMEM) was used to analyse the pharmacokinetics of ICL670 and Fe-[ICL670]2 from 18 subjects who received daily oral doses of ICL670 (10, 20 or 40 mg/kg) for 12 days. The relationship between ICL670 exposure and the efficacy variable faecal iron excretion was explored.
Results: A three-compartment pharmacokinetic model (including two-compartments for ICL670 and one-compartment for Fe-[ICL670]2 formation) best described the ICL670-Fe-[ICL670]2 pharmacokinetics. ICL670 apparent clearance (CL/F), apparent volume of distribution (V1/F) and Fe-[ICL670]2 apparent clearance (CL/Fm) and apparent volume of distribution (V3/Fm) were 2.9 L/h, 31.6 L, 12.1 L/h and 16.3 L respectively. An empirical linear effect model was fitted to describe the relationship between exposure to ICL670 (daily ICL670 AUC) and daily faecal iron excretion. The linear relationship was described with an intercept of 2.53 mg/L and slope of 3.26 mg/L/h.
Conclusions: The analysis provides a model which characterises the pharmacokinetics of ICL670 and Fe-[ICL670]2 in plasma and the effect of ICL670 administration on feacal iron excretion in beta-thalassaemia patients.
Reference: PAGE 13 (2004) Abstr 546 [www.page-meeting.org/?abstract=546]
Poster: poster