Zolmed/Zolmed Forte Mechanism of Action

Pharmacology: Pharmacodynamics: Mechanism of Action: The antimicrobial activity of the combination of trimethoprim and sulfamethoxazole results from its actions in two steps of the enzymatic pathway for the synthesis of tetrahydrofolic and sulfonamides inhibits the incorporation of PABA into folic acid, and trimethoprim presents the reduction of dihydrofolate to tetrahydrofolate, the latter in the form of folate essential for one carbon transfer reactions. The synergistic interaction between sulfonamide and trimethoprim is predictable from their respective mechanism. There is an equal to the ratio of the concentration of the two agents for synergism, and this is equal to the ratio of the inhibitory concentration of the drugs acting independently. The most effective ratio for the greatest number of the microorganism 20 parts of sulfamethoxazole to one part of trimethoprim. The minimal inhibitory concentration for sulfamethoxazole alone is 3 mcg/mL, while that for trimethoprim is 0.3 mg/mL. When the combination is tested a ratio of 20.1 inhibitory concentrations and 0.1 mcg/mL and 0.85 mcg/mL, respectively the combination is actually bactericidal for one microorganism.
Bacterial Resistance: Sulfamethoxazole is lower than it is to either of the agent alone. Since microorganism that has acquired resistance to one of the components may still be killed by the other. Trimethoprim-resistant microorganisms may arise by mutations. Resistance in gram negative bacteria is often associated with the acquisition of a plasmid that codes for an altered dihydrofolate reductase. Sulfamethoxazole increased only from 0.2% to 1.5% over a period.
Pharmacokinetics: Cotrimoxazole is rapidly ad well absorbed from the gastrointestinal tract and peak plasma concentrations are reached between 1 to 4 hours after an oral dose; effective plasma concentration are maintained for up to 24 hours after an oral therapeutic dose. Steady-state concentrations are reached after dosing for 2 to 3 days. Plasma concentrations of trimethoprim and sulfamethoxazole ae generally around the optimal ratio of 1:20 although they may vary from 1:20 to 1:30 or more.
The ratio of the to drugs is usually much lower in the tissues (often around 1:2 to 1:5) since trimethoprim, the more lipophilic drug penetrates many tissues better than sulfamethoxazole and has much larger volume of distribution. In urine, the ratio may vary from 1:1 to 1:5 depending on the pH. Cotrimoxazole is excreted mainly by the kidneys through both glomerular filtration and tubular secretion; about 505 is excreted in the urine within 24 hours as uchanged drug.