2002
   Paris, France

Pooled PK analysis of Interferon-beta-1a (Rebif), data obtained in healthy subjects and in patients.

Sophie Glatt1, Olivier Petricoul1, Ciara Rossier2, Quyen T.X Nguyen2, Alain Munafo2, Timothy Goggin2, Mauro Buraglio2, and Eliane Fuseau1

1 EMF-Consulting, France; 2 SERONO SA International, Geneva switzerland

Introduction and Objectives: Recombinant human interferon-beta-1a (Rebif) is currently used for the treatment of multiple sclerosis and is being investigated in other autoimmune diseases. The objective of the present PK analysis is to integrate all the available knowledge about the pharmacokinetics of interferon-beta-1a (IFN) in healthy subjects and in patients, including the relationships between pharmacokinetics and covariates such as route of administration, formulation, dosage, hematological parameters, demographics, etc…

Methods: Rich and sparse data were available from healthy subjects and patients who received Rebif. A total of 435 subjects from 11 studies were included in the analysis. Rebif was administered at the doses of 22 µg, 44 µg, 66 µg and 88 µg by various routes (IV, SC and IM). The concentration of IFN was determined using a Toray enzyme linked immunosorbant assay (Elisa). The limits of quantification and detection were set to 2.5 IU/mL and 1 UI/mL, respectively. Concentration-time pooled data were analyzed by a population approach using NONMEM.

Results: The SC, IM and IV data were fitted simultaneously to a 2-compartment model. Combinations of first order and mixed absorption were investigated to describe the absorption process. The residual error model was proportional and relevant covariates were explored once the base model has been established. The results of this analysis will be presented in the poster.