Pharmacokinetic study of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies

W. C. Zamboni, S. Strychor, L. Maruca, S. Ramalingam, B. A. Zamboni, H. Wu, D. M. Friedland, R. P. Edwards, R. G. Stoller, C. P. Belani, R. K. Ramanathan

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)519-526
Number of pages8
JournalClinical pharmacology and therapeutics
Volume86
Issue number5
DOIs
StatePublished - Nov 2009

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Pharmacokinetic study of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies'. Together they form a unique fingerprint.

Cite this