title: Pharmacokinetics and urinary excretion of vincristine sulfate liposomes injection in metastatic melanoma patients.
abstract: Vincristine sulfate liposomes injection (VSLI) is a liposomal formulation of vincristine encapsulated in sphingosomes composed of sphinogomyelin and cholesterol (58/42; mol/mol). The pharmacokinetics and urinary excretion of VSLI were evaluated in 12 patients with metastatic melanoma after single-dose (2.0 mg/m2 every 2 weeks = 1 cycle) and multiple-dose (cycle 3, pharmacokinetics only) administrations (intravenous infusion over 1 hour). After VSLI infusion, total (released and encapsulated) vincristine concentrations in plasma remained relatively constant for 3 to 12 hours and thereafter declined, with interpatient variability seen in the rate of decline resulting in monoexponential or biexponential profiles. The area under the plasma concentration-time curve from time zero to infinity of total vincristine in plasma ranged from 4933 to 40495 h.ng/mL and total clearance ranged from 131 to 445 mL/h. The volume of distribution at steady state was 2650 +/- 731 mL, indicating VSLI was mainly confined within the plasma. The released vincristine concentrations in plasma were below the level of quantitation in 95% of samples. The pharmacokinetic parameters were similar between cycles 1 and 3, and trough plasma levels of total vincristine were below the level of quantitation of 1 ng/mL. Approximately 8% of the injected dose was excreted in the urine as unchanged vincristine (7%) or N-desformylvincristine (0.8%). Overall, VSLI exhibited a longer circulation half-life and higher area under the plasma concentration-time curve compared to conventional vincristine, whereas its route of elimination remained unchanged.
authors.affiliation: Department of Melanoma Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 430, Houston, TX 77030, USA. abedikia@mdanderson.org
authors.forename: Agop Y
authors.initials: AY
authors.lastname: Bedikian
authors.forename: Anna
authors.initials: A
authors.lastname: Vardeleon
authors.forename: Teresa
authors.initials: T
authors.lastname: Smith
authors.forename: Susan
authors.initials: S
authors.lastname: Campbell
authors.forename: Rostam
authors.initials: R
authors.lastname: Namdari
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy / Q000473:pathology / Q000652:urine*; D008875:Middle Aged; D012878:Skin Neoplasms / Q000652:urine; D014750:Vincristine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D008081:Liposomes; D014750:Vincristine