Factors affecting the pharmacokinetics of pegylated liposomal doxorubicin in patients

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 a...

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Bibliographic Details
Published in:Cancer chemotherapy and pharmacology 2012-01, Vol.69 (1), p.43-50
Main Authors: La-Beck, Ninh M., Zamboni, Beth A., Gabizon, Alberto, Schmeeda, Hilary, Amantea, Michael, Gehrig, Paola A., Zamboni, William C.
Format: Article
Language:English
Subjects:
Adult
Age Factors
Aged
Antibiotics, Antineoplastic - administration & dosage
Antibiotics, Antineoplastic - pharmacokinetics
Antibiotics, Antineoplastic - therapeutic use
Antineoplastic agents
Biological and medical sciences
Body Surface Area
Cancer Research
Doxorubicin - administration & dosage
Doxorubicin - analogs & derivatives
Doxorubicin - pharmacokinetics
Doxorubicin - therapeutic use
Female
Humans
Male
Medical sciences
Medicine
Medicine & Public Health
Middle Aged
Monocytes - metabolism
Neoplasms - drug therapy
Neoplasms - pathology
Oncology
Original Article
Pharmacology. Drug treatments
Pharmacology/Toxicology
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - pharmacokinetics
Polyethylene Glycols - therapeutic use
Sarcoma, Kaposi - drug therapy
Sarcoma, Kaposi - pathology
Sex Factors
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Summary: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
ISSN:0344-5704
1432-0843
DOI:10.1007/s00280-011-1664-2