Dose selection and population pharmacokinetics of PEG‐Intron in patients with chronic myelogenous leukaemia

Aims To assess the dose selection using population pharmacokinetics of Pegylated Intron‐α2b (PEG‐Intron) in patients with chronic myelogenous leukaemia (CML). Methods PEG‐Intron 3–6 µg kg−1 was administered subcutaneously once a week and blood samples were collected up to 48 weeks of treatment. A total of 624 samples collected from 137 patients were included in the analysis. Nonlinear mixed‐effects modelling was used to analyse the sparsely sampled concentration data from a clinical efficacy trial. Covariates in the analysis included weight, sex, age, race, serum creatinine and estimated creatinine clearance (CLcr). Results The apparent clearance of PEG‐Intron decreased after repeated dosing. The clearance at treatment week 4 was 42.3 l day−1 (patients with CLcr 120 ml min−1) with interpatient variability 30%. At treatment week 48, the clearance value was reduced to 69% of its week 4 value. CLcr, a composite variable calculated from body weight, sex, age and serum creatinine, had a small but statistically significant influence on the clearance of PEG‐Intron. The clearance of PEG‐Intron in patients with CML was 40% higher than that of hepatitis C virus‐infected patients. Conclusion The dose of PEG‐Intron 6.0 µg kg−1 week−1 appeared appropriate in the treatment of patients with CML.