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.

Answer 2

Co-trimoxazole combines trimethoprim and sulfamethoxazole in a fixed dose ratio designed so that, once both drugs are absorbed and distributed in the body, their blood levels line up near the ratio that gives the strongest combined antibacterial effect. Working through the pharmacokinetic reasoning shows why the blood ratio differs from the dosing ratio.

1. 1:1: A 1:1 blood ratio would only happen if both drugs were cleared and distributed identically, but sulfamethoxazole has a much larger volume of distribution and different clearance than trimethoprim, so this option ignores those pharmacokinetic differences.
2. 1:5: This is actually the ratio the two drugs are combined in as a dosage form, trimethoprim to sulfamethoxazole, not the ratio they reach in the blood after absorption. Confusing the dose ratio with the blood ratio makes this option incorrect.
3. 1:10: This falls between the dosing ratio and the true blood ratio but does not match either figure that is actually used or measured for this combination.
4. 1:20: Because sulfamethoxazole is cleared and distributed differently from trimethoprim, dosing them at 1:5 results in blood levels that shift further apart, reaching close to a 1:20 ratio of trimethoprim to sulfamethoxazole. This blood ratio happens to be near the ratio shown in lab studies to give the strongest synergistic antibacterial effect against susceptible organisms.

The dosing ratio of 1:5 is deliberately chosen so that pharmacokinetic differences push the actual blood concentration ratio out to about 1:20.

So the correct answer is 1:20.