Question

Trimethoprim-sulfonamides are formulated in a ratio of 1:5 (trimethoprim:sulfonamide). In the animal, it is usually cited that the optimum ratio to produce antibacterial activity is:

• A. 1:10
• B. 1:15
• C. 1:20
• D. 1:12

Hint:

Keep these two ratios clear for competitive exams:
- Formulation Ratio (in the tablet/injection) = 1:5.
- Tissue/Serum Therapeutic Ratio (in the body) = 1:20.

Answer 1

The Correct Option is C

Step 1: Understanding the Concept:
Trimethoprim and sulfonamides act synergistically to block sequential steps in the bacterial folate synthesis pathway (sequential double blockade).
Due to differences in their pharmacokinetic profiles (volume of distribution and clearance rates), they must be formulated in a specific ratio to achieve the optimal synergistic concentration ratio in vivo.

Step 2: Detailed Explanation:
Let us analyze the concentration dynamics of these drugs:
- Formulation Ratio: Co-trimoxazole and similar combinations are formulated in a 1:5 ratio of trimethoprim to sulfonamide (for example, 80 mg trimethoprim with 400 mg sulfamethoxazole).
- In vivo Target Ratio: Trimethoprim is highly lipophilic and has a much larger volume of distribution compared to sulfonamides, leaving the plasma compartment rapidly.
- To achieve the optimal synergistic concentration ratio of 1:20 (trimethoprim to sulfonamide) in the blood and tissue fluids (which is the ratio that produces the maximum antibacterial synergy), the 1:5 dose formulation is required.

Step 3: Final Answer:
Thus, the optimum ratio required in the animal tissue/blood to produce synergistic antibacterial activity is 1:20.