Published in:
01-01-2012 | Original Article
Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients
Published in: Cancer Chemotherapy and Pharmacology | Issue 1/2012
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Purpose
There is significant inter-patient variability in the pharmacokinetics of pegylated liposomal doxorubicin (PLD). Identification of factors affecting the pharmacokinetics of PLD would enable personalization of therapy. We previously reported that age, gender, body composition, and monocytes affect the clearance of other liposomal agents. Therefore, we evaluated how these factors affect the pharmacokinetics of PLD.
Methods
Pharmacokinetic studies of PLD were performed as part of phase I and II studies in 70 patients with solid tumors or Kaposi’s sarcoma. The effects of monocyte count, age, gender, and body composition on PLD clearance were examined.
Results
There was a 15.3-fold variability in PLD clearance. Body surface area-based dosing did not significantly reduce the variability in PLD clearance. The mean ± SD clearance for patients <60 years old and ≥60 years old were 54.6 ± 28.5 and 23.3 ± 10.8 mL/h/m2, respectively (P < 0.0001), and for female and male patients were 23.7 ± 18.8 and 55.6 ± 26.8 mL/h/m2, respectively (P < 0.0001). A reduction in pre-cycle monocyte count was associated with a greater reduction in PLD clearance.
Conclusions
Age, gender, and monocyte counts appear to correlate with PLD clearance. Further investigation of the association between these factors, PLD pharmacokinetics, and clinical outcomes (efficacy and toxicity) is warranted. These effects on the pharmacokinetics of PLD may be an approach for personalizing PLD therapy and may affect other pegylated liposomes and nanoparticle agents.