A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Matulane Pharmacology, Pharmacokinetics, Studies, Metabolism - Procarbazine
Matulane Pharmacology, Pharmacokinetics, Studies, Metabolism - Procarbazine
CLINICAL PHARMACOLOGY
The precise mode of cytotoxic action of procarbazine has not been clearly
defined. There is evidence that the drug may act by inhibition of protein,
RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit
transmethylation of methyl groups of methionine into t-RNA. The absence
of functional t-RNA could cause the cessation of protein synthesis and
consequently DNA and RNA synthesis. In addition, procarbazine may directly
damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the
drug, may attack protein sulfhydryl groups contained in residual protein
which is tightly bound to DNA.
Procarbazine is metabolized primarily in the liver and kidneys. The drug
appears to be auto-oxidized to the azo derivative with the release of
hydrogen peroxide. The azo derivative isomerizes to the hydrazone, and
following hydrolysis splits into a benzylaldehyde derivative and methylhydrazine.
The methylhydrazine is further degraded to CO2 and CH4
and possibly hydrazine, whereas the aldehyde is oxidized to N-isopropylterephthalamic
acid, which is excreted in the urine.
Procarbazine is rapidly and completely absorbed. Following oral administration
of 30 mg of 14C-labeled procarbazine, maximum peak plasma radioactive
concentrations were reached within 60 minutes.
After intravenous injection, the plasma half-life of procarbazine is
approximately 10 minutes. Approximately 70% of the radioactivity is excreted
in the urine as N-isopropylterephthalamic acid within 24 hours
following both oral and intravenous administration of 14C-labeled
procarbazine.
Procarbazine crosses the blood-brain barrier and rapidly equilibrates
between plasma and cerebrospinal fluid after oral administration.
top
