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
Fioricet Pharmacology, Pharmacokinetics, Studies, Metabolism - Butalbital, Acetaminophen and Caffeine
Fioricet Pharmacology, Pharmacokinetics, Studies, Metabolism - Butalbital, Acetaminophen and Caffeine
CLINICAL PHARMACOLOGY
This combination drug
product is intended
as a treatment for
tension headache.
It consists of a fixed combination of butalbital, acetaminophen
and caffeine. The role
each component plays
in the relief of the
complex of symptoms
known as tension headache
is incompletely understood.
Pharmacokinetics
The behavior of the
individual components is described below.
Butalbital: Butalbital is well absorbed from the
gastrointestinal tract and is expected to distribute to most tissues
in the body. Barbiturates in general may appear in breast
milk and readily cross
the placental barrier.
They are bound to plasma
and tissue proteins to
a varying degree and
binding increases directly as a function
of lipid solubility.
Elimination of butalbital is primarily via
the kidney (59% to 88%
of the dose) as unchanged drug
or metabolites. The plasma
half-life is about
35 hours. Urinary excretion
products include parent
drug (about 3.6% of the
dose), 5- isobutyl-5-(2,3-dihydroxypropyl) barbituric acid
(about 24% of the dose), 5-allyl-5(3-hydroxy-2-methyl-1-propyl)
barbituric acid (about
4.8% of the dose), products with the barbituric acid
ring hydrolyzed with excretion
of urea (about 14% of the
dose), as well as unidentified materials. Of the material
excreted in the urine,
32% is conjugated. (See OVERDOSAGE
for toxicity information.)
Acetaminophen: Acetaminophen is rapidly absorbed
from the gastrointestinal
tract and is distributed
throughout most body tissues.
The plasma half-life
is 1.25 to 3 hours, but may be increased by liver damage and following
overdosage. Elimination of acetaminophen
is principally by liver
metabolism (conjugation)
and subsequent renal excretion
of metabolites. Approximately 85% of an oral
dose appears in the urine
within 24 hours of administration, most as the glucuronide
conjugate, with small
amounts of other conjugates and unchanged drug. (See OVERDOSAGE
for toxicity information.)
Caffeine: Like most xanthines, caffeine
is rapidly absorbed and distributed in all body
tissues and fluids, including the CNS, fetal tissues, and breast
milk. Caffeine is cleared through metabolism
and excretion in the urine. The plasma
half-life is about
3 hours. Hepatic biotransformation prior to excretion
results in about equal amounts of 1-methyl-xanthine and 1-methyluric
acid. Of the 70% of the dose
that is recovered in the urine, only 3% is unchanged drug. (See
OVERDOSAGE for toxicity
information.)
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