title: Pharmacokinetics of CPX-351; a nano-scale liposomal fixed molar ratio formulation of cytarabine:daunorubicin, in patients with advanced leukemia.
abstract: Forty-eight patients received CPX-351 (liposome-encapsulated cytarabine:daunorubicin at a 5:1 molar ratio) every other day for 3 doses at 10 dose levels. Pharmacokinetic parameters were dose-independent and exhibited low inter-patient variability. CPX-351 showed a negligible distribution phase and prolonged mono-exponential first-order plasma elimination (t(1/2)∼24 h). The plasma ratio of 5:1 was maintained at all dose levels. Nearly all of the detectable cytarabine and daunorubicin in circulation following CPX-351 administration was in the form of liposome encapsulated drug. Dose-dependent hematopoietic effects had early onset with cytopenias at 12 units/m(2), and a gradual increase in frequency and severity, until single induction complete response was achieved at 43 units/m(2). Non-hematologic effects had onset by 24 units/m(2) with shallow dose-response until maximum frequency and severity were observed at the 101-134 units/m(2) dose levels. Single induction response occurred over a 2.3-fold range of doses indicating that CPX-351 may be useful at high doses for patients suitable for intensive chemotherapy and at reduced doses for patients at increased risk of treatment-related mortality. The unique pharmacologic features of CPX-351 contribute to its promising antileukemic efficacy.
authors: Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, NY, USA.
authors: E J
authors: EJ
authors: Feldman
authors: J E
authors: JE
authors: Kolitz
authors: J M
authors: JM
authors: Trang
authors: B D
authors: BD
authors: Liboiron
authors: C E
authors: CE
authors: Swenson
authors: M T
authors: MT
authors: Chiarella
authors: L D
authors: LD
authors: Mayer
authors: A C
authors: AC
authors: Louie
authors: J E
authors: JE
authors: Lancet
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000188:drug therapy*; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D036103:Nanotechnology; D011379:Prognosis
chemical_list: D008081:Liposomes; D003561:Cytarabine; D003630:Daunorubicin