Medical Pharmacology Chapter 33-34: Anticancer Drugs
Natural Products: Vinca Alkaloids
Vinorelbine (Nevelbine, VRL) exhibits pharmacological properties similar to other vinca alkaloids.
Accordingly, after rapid IV administration, vinorelbine plasma levels decline first rapidly and then with a slow elimination phase exhibiting a terminal half-life in the range of 20-50 hours, overall a triphasic curve.8
Vinorelbine was the initial vinca alkaloid exhibiting oral activity, showing comparable pharmacokinetic properties to the IV administered agent.
This formulation is available in certain countries with drug oral bioavailability estimated about 40%.8
Vinorelbine is substantially bound, about 85%, to plasma proteins, mainly α1-acid glycoprotein, albumin and lipoproteins.
Vinorelbine also binds to platelets.
Except for the CNS (central nervous system) vinorelbine exhibits wide distribution, penetrating nearly all tissues.10
The underlying reason for why distribution is found in the lipophilic character of vinorelbine.
Vinorelbine lipophilicity (manifest as ready partitioning into and through cell membrane lipid bilayers) is noted among the highest of the vinca alkaloids.10
Vinorelbine is primarily (as much as 80%) excreted in the feces following hepatic metabolism. The primary cytochrome P450 isoform responsible for vinorelbine biotransformation is CYP3A.
Urinary excretion accounts for about 20% of drug disposition, mainly in the form of the parent compound.
Most metabolites do not exhibit antineoplastic activity; however, the deacetyl-VRL metabolite may exhibit comparable pharmacological activity as the parent compound.10
Vinorelbine exhibits antineoplastic activity against both breast cancer and non-small cell lung cancer (SCLC).1
Since vinorelbine is metabolized (detoxified) mainly by the liver, a patient exhibiting hepatic dysfunction may require dosage alteration.
Dosage change does not appear required in cases of compromised kidney function. 8
Vinca alkaloids toxicities have been described earlier.
Vinorelbine administration is associated with myelosuppression (similar to that seen with vinblastine and by contrast to the neurotoxicity as the prominent vincristine toxicity).8
The most prominent myelosuppressive toxicity associated with vinorelbine is granulocytopenia.1
Limited thrombocytopenia may also be noted.1
|Alkylating agents||Antitumor antibiotics||Anthracyclines||Taxane||Vinca alkaloids||Non-classical alkylating agent|