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
Rifamate Pharmacology, Pharmacokinetics, Studies, Metabolism - Rifampin and Isoniazid
Rifamate Pharmacology, Pharmacokinetics, Studies, Metabolism - Rifampin and Isoniazid
CLINICAL PHARMACOLOGY
ACTIONS
Rifampin
Rifampin inhibits DNA-dependent RNA polymerase activity in susceptible cells.
Specifically, it interacts with bacterial RNA polymerase but does not inhibit
the mammalian enzyme. This is the mechanism of action by which rifampin exerts
its therapeutic effect. Rifampin cross resistance has only been shown with other
rifamycins.
In a study of 14 normal human adult males, peak blood levels of rifampin occured
1 1 / 2 to 3 hours following oral administration of two
RIFAMATE capsules. The peaks ranged from 6.9 to 14 mcg/ml with an average of
10 mcg/ml.
In normal subjects the T 1 / 2 (biological half-life)
of rifampin in blood is approximately 3 hours. Elimination occurs mainly through
the bile and, to a much lesser extent, the urine.
Isoniazid
Isoniazid acts against actively growing tubercle bacilli.
After oral administration isoniazid produces peak blood levels within 1 to
2 hours which decline to 50% or less within 6 hours. It diffuses readily into
all body fluids (cerebrospinal, pleural, and ascitic fluids), tissues, organs,
and excreta (saliva, sputum, and feces). The drug also passes through the placental
barrier and into milk in concentrations comparable to those in the plasma. From
50 to 70% of a dose of isoniazid is excreted in the urine in 24 hours.
Isoniazid is metabolized primarily by acetylation and dehydrazination. The
rate of acetylation is genetically determined. Approximately 50% of Blacks and
Caucasians are "slow inactivators"; the majority of Eskimos and Orientals are
"rapid inactivators."
The rate of acetylation does not significantly alter the effectiveness of isoniazid.
However, slow acetylation may lead to higher blood levels of the drug, and thus
an increase in toxic reactions.
Pyridoxine deficiency (B 6 ) is sometimes observed in adults with
high doses of isoniazid and is considered probably due to its competition with
pyridoxal phosphate for the enzyme apotryptophanase.
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