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Pharmacokinetic Study of Pegylated Liposomal CKD‐602 (S‐CKD602) in Patients With Advanced Malignancies
Author(s) -
Zamboni WC,
Strychor S,
Maruca L,
Ramalingam S,
Zamboni BA,
Wu H,
Friedland DM,
Edwards RP,
Stoller RG,
Belani CP,
Ramanathan RK
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2009.141
Subject(s) - pharmacokinetics , medicine , pharmacology , drug , liposome , disposition , clinical pharmacology , clearance , urology , chemistry , psychology , social psychology , biochemistry
S‐CKD602 is a pegylated liposomal formulation of CKD‐602. This study is the first to evaluate the factors affecting the high interpatient variability in the pharmacokinetic disposition of S‐CKD602. S‐CKD602 was administered intravenously (i.v.) every 3 weeks as part of a phase I study. Pharmacokinetics studies of the liposomal encapsulated and released CKD‐602 in plasma were performed. The pharmacokinetic variability of S‐CKD602 is associated with both linear and nonlinear clearances. Patients ≥60 years of age have a 2.7‐fold higher exposure of S‐CKD602 as compared with patients <60 years of age ( P = 0.02). Patients with a lean body composition have a higher plasma exposure of S‐CKD602 ( P = 0.02). Patients who have received prior therapy with pegylated liposomal doxorubicin (PLD) have a 2.2‐fold higher exposure of S‐CKD602 as compared with patients who have not received PLD ( P = 0.045). Prolonged exposure of the encapsulated drug in plasma over 1–2 weeks provides significant pharmacologic advantages. The high interpatient variability in the pharmacokinetic disposition of S‐CKD602 was associated with age, body composition, saturable clearance, and prior PLD therapy. Clinical Pharmacology & Therapeutics (2009) 86 5, 519–526. doi: 10.1038/clpt.2009.141