Dose selection and population pharmacokinetics of PEG-Intron in patients with chronic myelogenous leukaemia.
OBJECTIVE
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.


CONCLUSIONS
The dose of PEG-Intron 6.0 microg kg(-1) week(-1) appeared appropriate in the treatment of patients with CML.
Gupta
Samir
S
Schering-Plough Research Institute, Kenilworth, NJ, USA. samir.gupta@spcorp.com
Jen
Juif
J
Kolz
Karen
K
Cutler
David
D
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b