Question

Blood concentration ratio of the combination of trimethoprim and sulfamethoxazole after being given in a 1:5 ratio is

• A. 1:1
• B. 1:5
• C. 1:10
• D. 1:20

Hint:

Trimethoprim inhibits dihydrofolate reductase, while sulfamethoxazole inhibits dihydropteroate synthase—together they block folate synthesis, leading to synergistic action.

Answer 1

The Correct Option is D

Trimethoprim and sulfamethoxazole are combined in a fixed-dose formulation due to their synergistic antibacterial activity, often referred to as co-trimoxazole. The combination is typically administered in a 1:5 ratio by weight (trimethoprim:sulfamethoxazole) to achieve an optimal blood concentration ratio of 1:20. This adjustment is required because of pharmacokinetic differences between the two drugs: - Sulfamethoxazole has a much higher volume of distribution and faster clearance than trimethoprim.
- To ensure both drugs achieve their desired therapeutic concentration at the site of action, the ratio of 1:5 in the dosage form compensates for these differences.
- Once administered, trimethoprim accumulates more in tissues, while sulfamethoxazole maintains higher plasma levels, resulting in a plasma (blood) concentration ratio of approximately 1:20 (trimethoprim:sulfamethoxazole).
This blood concentration ratio is ideal for their combined bacteriostatic effect, targeting sequential steps in folic acid synthesis in bacteria.