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
Gantanol Pharmacology, Pharmacokinetics, Studies, Metabolism - Sulfamethoxazole
Gantanol Pharmacology, Pharmacokinetics, Studies, Metabolism - Sulfamethoxazole
CLINICAL PHARMACOLOGY
Sulfamethoxazole is rapidly absorbed following oral administration. It
exists in the blood as unbound, protein-bound, metabolized and conjugated
forms. The metabolism of sulfamethoxazole occurs predominately by N4-acetylation,
although the glucuronide conjugate has been identified. The free form
is considered to be the therapeutically active form. Approximately 70%
of sulfamethoxazole is bound to plasma proteins; of the unbound portion,
80% to 90% is in the nonacetylated form.
Following a single 1-g oral dose in 12 volunteer male subjects, the mean
peak plasma concentration of 38 µg/mL of intact sulfamethoxazole
was achieved by 2 hours. The mean half-life of sulfamethoxazole is approximately
10 hours. However, patients with severe-ly impaired renal function, as
shown by a creatinine clearance of less than 30 mL/minute, exhibit an
increase in the half-life of sulfamethoxazole, requiring dosage regimen
adjustment.
Sulfamethoxazole is excreted primarily by the kidneys chiefly through
glomerular filtration but also through tubular secretion. Urine concentrations
of sulfamethoxazole are considerably higher than are the concentrations
in blood. Eighty percent to 100% of the dose is excreted in the urine
as total sulfamethoxazole, of which 30% is intact drug with the remaining
as the N4-acetylated metabolite.
Sulfamethoxazole diffuses into cerebrospinal fluid, with peak concentrations
occurring at 8 hours and reaching approximately 14% of simultaneous plasma
concentrations. The drug has also been shown to distribute to aqueous
humor, vaginal fluid and middle ear fluid; it also passes the placental
barrier and is excreted in breast milk.
Microbiology
The systemic sulfonamides are bacteriostatic agents and the spectrum
of activity is similar for all. Sulfonamides inhibit bacterial synthesis
of dihydrofolic acid by competing with para-aminobenzoic acid
(PABA). Resistant strains are capable of utilizing folic acid precursors
or preformed folic acid.
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