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.