Pharmacokinetics and safety of Marqibo (vincristine sulfate liposomes injection) in cancer patients with impaired liver function

Agop Y Bedikian; Jeffrey A Silverman; Nicholas E Papadopoulos; Kevin B Kim; Anne E Hagey; Anna Vardeleon; Wen-Jen Hwu; Jade Homsi; Michael Davies; Patrick Hwu

doi:10.1177/0091270010381499

Pharmacokinetics and safety of Marqibo (vincristine sulfate liposomes injection) in cancer patients with impaired liver function

J Clin Pharmacol. 2011 Aug;51(8):1205-12. doi: 10.1177/0091270010381499. Epub 2010 Oct 26.

Authors

Agop Y Bedikian¹, Jeffrey A Silverman, Nicholas E Papadopoulos, Kevin B Kim, Anne E Hagey, Anna Vardeleon, Wen-Jen Hwu, Jade Homsi, Michael Davies, Patrick Hwu

Affiliation

¹ Department of Melanoma Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.

PMID: 20978276
DOI: 10.1177/0091270010381499

Abstract

Marqibo (vincristine sulfate liposome injection, VSLI) is a novel liposomal formulation of vincristine sulfate (VCR) being developed for the systemic treatment of cancer. This study evaluated the pharmacokinetics (PK) of Marqibo in subjects with melanoma and impaired hepatic function. Calculated PK parameters were similar in subjects with impaired liver function compared with those in subjects with adequate liver function. Subjects with impaired liver function universally had a monoexponential total plasma VCR concentration versus time decline, whereas two thirds of subjects with adequate liver function had a biexponential decline profile. Because one third of subjects with normal hepatic function demonstrated monoexponential disposition, lack of biexponential disposition in the hepatically impaired subjects cannot be clearly attributed to liver impairment. VSLI was generally well tolerated in all subjects.

Trial registration: ClinicalTrials.gov NCT00506142.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antineoplastic Agents, Phytogenic / administration & dosage*
Antineoplastic Agents, Phytogenic / adverse effects
Antineoplastic Agents, Phytogenic / blood
Antineoplastic Agents, Phytogenic / pharmacokinetics*
Ascites / physiopathology
Female
Half-Life
Hepatic Insufficiency / etiology*
Humans
Liposomes
Liver Neoplasms / drug therapy
Liver Neoplasms / metabolism
Liver Neoplasms / physiopathology*
Liver Neoplasms / secondary
Male
Melanoma / blood
Melanoma / drug therapy*
Melanoma / metabolism
Melanoma / secondary
Metabolic Clearance Rate
Middle Aged
Neoplasm Staging
Pharmaceutical Vehicles / therapeutic use
Skin Neoplasms / blood
Skin Neoplasms / complications
Skin Neoplasms / drug therapy
Skin Neoplasms / metabolism
Survival Analysis
Tubulin Modulators / administration & dosage
Tubulin Modulators / adverse effects
Tubulin Modulators / blood
Tubulin Modulators / pharmacokinetics
Uveal Neoplasms / blood
Uveal Neoplasms / complications
Uveal Neoplasms / drug therapy
Uveal Neoplasms / metabolism
Vincristine / administration & dosage*
Vincristine / adverse effects
Vincristine / blood
Vincristine / pharmacokinetics*

Substances

Antineoplastic Agents, Phytogenic
Liposomes
Pharmaceutical Vehicles
Tubulin Modulators
Vincristine

Associated data

ClinicalTrials.gov/NCT00506142