ArticleLipids in health and disease2016
The effect of increased lipoproteins levels on the disposition of vincristine in rat.
Article in Lipids in health and disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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4 authors at 2 institutions in 2 countries.
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No grant is acknowledged in the PubMed record.
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.
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