|Gama Nindya .S 128114093 | Lucia Effelin Cindya.

D 128114096 | Dionisius Laffyanto 128114100

|Stanislaus Kris Bangkit Tri Putra 128114101 | Bertha Nathania 128114102 | Vicky Wijoyo 128114131|

Vinblastine
Brand name of Vinblastine is Velban .This drug
is anticancer agent. Vinblastine is used for the
treatment
of
Hodgkins
disease,
lymphoma,testicular cancer, and breast cancer.
In people with HIV, it used for the treatment of
Kaposis sarcoma (KS).
Mechanism : VBL metabolism significantly
paralleled the erythromycin-JV-demethylase
activity (mediated by CYP3A4) but not the
aniline metabolism (a substrate of P450 2E).
The direct inhibition experiment of VBL
biotransformation showed that only the
antihuman P450 3A antibody inhibited the
metabolism of VBL, confirming the involvement
of cytochrome P450 3A in this biotransformation. Moreover, a highly significant correlation was
found between the level of P450 3A and the metabolism of VBL. VBL metabolism was correlated
with the level of CYP3A4-specific mRNA, evaluated by hybridization with a synthetic oligonucleotide.
The oligonucleotide recognized the two members of the CYP3A4 subfamily (nflO and nf25). Reversal
of the antitumor effect of Vinblastine sulfate by glutamic acid or tryptophan has been observed. In
addition, glutamic acid and aspartic acid have protected mice from lethal doses of Vinblastine
sulfate. Aspartic acid was relatively ineffective in reversing the antitumor effect.
Other studies indicate that Vinblastine sulfate has an effect on cell-energy production
required for mitosis and interferes with nucleic acid synthesis. The mechanism of action of
Vinblastine has been related to the inhibition of microtubule formation in the mitotic spindle,
resulting in an arrest of dividing cells at the metaphase stage.
Metabolism : Tissue-culture studies suggest an interference with metabolic pathways of amino acids
leading from glutamic acid to the citric acid cycle and to urea.
The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450
isoenzymes in the CYP 3A subfamily. This metabolic pathway may be impaired in patients with
hepatic dysfunction or who are taking concomitant potent inhibitors of these isoenzymes such as
erythromycin.
References :
Delaney, Martin, 1998, HIV Drug Book, http://books.google.co.id/ books?id=v8itp3BnM9gC&pg=
PA144&dq=brand+names+vinblastine&hl=id&sa=X&ei=LJRyVMGVFYq0uASjqYDACw&ved=0C
BwQ6AEwAA#v=onepage&q=brand%20names%20vinblastine&f=false diakses pada tanggal
24 November 2014 pukul 11.40 WIB.
Zhou, Pan, 1993, Involvement of Human Liver Cytochrome P450 3A in Vinblastine Metabolism: Drug
Interactions, Cancer Research, Vol. 53, pp. 5121-5126.
http://www.drugs.com/pro/vinblastine.html