title: Pharmacokinetic study of pegylated liposomal CKD-602 (S-CKD602) in patients with advanced malignancies.
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 > or =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.
authors.affiliation: Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. zamboni@email.unc.edu
authors.forename: W C
authors.initials: WC
authors.lastname: Zamboni
authors.forename: S
authors.initials: S
authors.lastname: Strychor
authors.forename: L
authors.initials: L
authors.lastname: Maruca
authors.forename: S
authors.initials: S
authors.lastname: Ramalingam
authors.forename: B A
authors.initials: BA
authors.lastname: Zamboni
authors.forename: H
authors.initials: H
authors.lastname: Wu
authors.forename: D M
authors.initials: DM
authors.lastname: Friedland
authors.forename: R P
authors.initials: RP
authors.lastname: Edwards
authors.forename: R G
authors.initials: RG
authors.lastname: Stoller
authors.forename: C P
authors.initials: CP
authors.lastname: Belani
authors.forename: R K
authors.initials: RK
authors.lastname: Ramanathan
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001823:Body Composition / Q000502:physiology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; C116963:belotecan; D011092:Polyethylene Glycols; D002166:Camptothecin