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-alpha2b (PEG-Intron) in patients with chronic myelogenous leukaemia (CML).

Methods: PEG-Intron 3-6 microg 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 microg kg(-1) week(-1) appeared appropriate in the treatment of patients with CML.