Abstract
BackgroundVincristine (VCR), an antineoplastic agent, is a key component in the treatment of acute lymphoblastic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms’ tumor diseases. Recently, high incidence of hyperlipidemia was reported to be associated with allogenic hematopoietic stem cell transplantation and VCR/L-asparaginase therapy.The aim of this study is to test the effects of incremental increase in lipoproteins levels on vincristine disposition in rat.MethodTo study VCR pharmacokinetics and protein binding, rats (n = 25) were assigned to three groups, normal lipidemic (NL), intermediate (IHL) and extreme hyperlipidemic (HL). Hyperlipidemia was induced by ip injection of (1 g/Kg) poloxamer 407 in rats. Serial blood samples were collected using the pre-inserted jugular vein cannula for 72 h post VCR (0.15 mg/Kg) i.v. dose. VCR unbound fractions in NL, IHL and HL plasma were determined using ultrafiltration kits.ResultsVCR demonstrated a rapid distribution phase (6–8 h) followed by a slower elimination phase with a mean elimination t½ of ~ 14 h. VCR exhibited moderate binding to plasma proteins ~ 83 %. It showed a relatively small Vc (~0.17 L/Kg) and a larger Vβ (1.53 L/Kg) indicating good tissue distribution. As the lipoproteins levels were increased, no significant changes were noted in VCR unbound fraction, plasma concentration, or volume of distribution indicating low affinity to lipoprotein binding. Induced HL also did not affect VCR elimination where similar VCR AUC0-∞, Cl and elimination phase t½ were reported along the different lipemic groups.ConclusionIncremental increase in lipoprotein levels resulted in no significant effect on VCR disposition as such ALL malignant lymphoma and allogenic hematopoietic stem cell transplantation patients need not to worry about HL-VCR interaction. Whether, HL can potentiate another drug-drug or drug-disease interaction involving VCR warrants further studying and monitoring to ensure therapeutic safety and efficiency.
Highlights
Vincristine (VCR), an antineoplastic agent, is a key component in the treatment of acute lymphoblastic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms’ tumor diseases
As the lipoproteins levels were increased, no significant changes were noted in VCR unbound fraction, plasma concentration, or volume of distribution indicating low affinity to lipoprotein binding
Incremental increase in lipoprotein levels resulted in no significant effect on VCR disposition as such Acute lymphoblastic leukemia (ALL) malignant lymphoma and allogenic hematopoietic stem cell transplantation patients need not to worry about HL-VCR interaction
Summary
Vincristine (VCR), an antineoplastic agent, is a key component in the treatment of acute lymphoblastic leukemia, lymphomas, rhabdomyosarcoma, neuroblastoma, and Wilms’ tumor diseases. Acute lymphoblastic leukemia (ALL), characterized by immature lymphoid cells in the bone marrow, peripheral blood and other organs, has a high incidence in USA and worldwide [1] It affects children and adults with median diagnosis age of 14 years [1]. Said R et al [1] vincristine (VCR) is an antineoplastic agent that acts by inhibiting microtubule formation in the miotic spindle causing cell death that may be accompanied by neurological side effect [2, 3] It represents a key component in the ALL in children and adults and is currently the backbone of the induction, intensification, and consolidation phases in the treatment of this disease [4].
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