Trimethoprim：5-[(3,4,5-trimethoxyphenyl)methyl]-2,4-pyrimidinediamine

Sulfamethoxazole：N1 - (5-methyl-3-isoxazolyl)

Absorption
Trimethoprim/sulfamethoxazole is rapidly absorbed following PO administration. T max is 1 to 4 hr. Steady state is achieved after 3 days.

Distribution
70% of sulfamethoxazole and 44% of trimethoprim is protein bound. Trimethoprim/sulfamethoxazole is distributed to sputum, vaginal fluid, and middle ear fluid. Trimethoprim/sulfamethoxazole passes the placental barrier and is excreted in human milk.

Metabolism
Metabolism of sulfamethoxazole is primarily by N 4 -acetylation. The principal metabolites of trimethoprim are the 1- and 3-oxides and the 3- and 4-hydroxy derivatives. The free forms are considered therapeutically active.

Elimination
Serum t ½ of sulfamethoxazole and trimethoprim is 10 hr and 8 to 10 hr, respectively. Trimethoprim/sulfamethoxazole is primarily eliminated by kidneys through glomerular filtration and tubular secretion. Urine concentrations are higher than blood concentrations.

Onset
Onset of action is 24 hr after administration.

Special Populations
Renal Function Impairment

Patients with severely impaired renal function exhibit an increase in the half lives of both components, requiring dosage adjustments.

Cyclosporine
May cause decrease in therapeutic effect of cyclosporine and increased risk of nephrotoxicity.

Methotrexate
May displace methotrexate from protein-binding sites, thus increasing free methotrexate levels.

Phenytoin
Trimethoprim may inhibit metabolism of phenytoin or other hydantoins.

Procainamide
Trimethoprim may inhibit renal elimination of procainamide and its metabolites.

Sulfonylureas
May increase hypoglycemic response to sulfonylureas because of displacement from protein-binding sites or inhibition of hepatic metabolism.

Warfarin
May cause prolonged PT.