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.

1.若出現皮疹，應中止使用本品。
2.輸液超過負荷是可能的，特別是當高劑量給予伴有基本心肺疾病之病人。
3.腎功能不良之患者應依上述指示調整劑量，且最好測量血漿濃度，應該維持適當的尿流量。
4.老年人：治療老年病人通常要特別小心，因有這群人對副作用較敏感且似乎蒙受較嚴重的效果。
5.當治療潛在性葉酸缺乏之病人應考慮補充葉酸，如老年人。
為了延長本品高濃度劑量也可以考慮補充葉酸。若延長本品治療，特別是對
於疑似葉酸代謝不良之病人，建議每個月做全血球計數，包括血小板的測量。死亡極罕見，然而以下的嚴重反應仍會導致死亡發生：Stevens-Johnson syndrome， Lyell's syndrome（中毒性皮上組織壞死）、猛爆性肝臟壞死、粒性白血球缺乏症、再生不能性貧血、血性惡液質、呼吸道過度興奮。需注意病人肝臟有嚴重實質的損傷時，對trimethoprim 和sulfamethoxazole 的吸收和代謝可能改變。
6.在G-6-PD 缺乏的病人可能會發生溶血症。投與本品給曾有嚴重過敏或支氣管性氣喘的病人應謹慎。
7.本品不應使用在因A 群β-溶血鏈球菌所引起的咽喉炎上，因其效果比
Penicillin 差。
8.Trimethoprim 會減少phenylalanine 代謝， 但這對有適當飲食控制的
phenylketonuric（苯酮酸尿症）病人沒有重大影響。
9.應避免投與本品於已知或疑似為紫質症危險群之病人，trimethoprim 和
sulphonamides 可能使紫質惡化（雖然沒有sulfamethoxazole 具體）。
10.有高血鉀風險的病人應密切監測血鉀濃度。