Pharmacokinetics and safety of Marqibo (vincristine sulfate liposomes injection) in cancer patients with impaired liver function.
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.
Bedikian
Agop Y
AY
Department of Melanoma Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Silverman
Jeffrey A
JA
Papadopoulos
Nicholas E
NE
Kim
Kevin B
KB
Hagey
Anne E
AE
Vardeleon
Anna
A
Hwu
Wen-Jen
WJ
Homsi
Jade
J
Davies
Michael
M
Hwu
Patrick
P
D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001201:Ascites / Q000503:physiopathology; D005260:Female; D006207:Half-Life; D048550:Hepatic Insufficiency / Q000209:etiology*; D006801:Humans; D008081:Liposomes; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology* / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009367:Neoplasm Staging; D014677:Pharmaceutical Vehicles / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D016019:Survival Analysis; D050257:Tubulin Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D014604:Uveal Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D014750:Vincristine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D000972:Antineoplastic Agents, Phytogenic; D008081:Liposomes; D014677:Pharmaceutical Vehicles; D050257:Tubulin Modulators; D014750:Vincristine