**Question:** A middle aged old man, with chronic renal failure is diagnosed to have sputum positive pulmonary tuberculosis. His creatinine clearance is 25m1/min. All of the following drugs need modification in doses except-

A. Ethambutol
B. Isoniazid
C. Rifampicin
D. Streptomycin

**Correct Answer:** C. Rifampicin

**Core Concept:** Modification of drug doses in patients with chronic renal failure

**Why the Correct Answer is Right:**

In patients with chronic renal failure, drug dosing needs to be adjusted to maintain therapeutic drug levels and avoid toxicity. The following drugs are commonly used in the treatment of pulmonary tuberculosis:

A. Ethambutol: Ethambutol is primarily eliminated via the liver, and renal function does not significantly impact its clearance. Hence, dosage adjustments are not necessary in patients with impaired renal function.

B. Isoniazid: Isoniazid is primarily eliminated via the liver (90% via liver and 10% via kidneys). Renal impairment does not significantly affect its clearance, so no dose adjustment is required.

D. Streptomycin: Streptomycin is a relatively low molecular weight drug, primarily eliminated by the kidneys. In patients with impaired renal function, the dosage needs to be reduced to avoid toxicity.

C. Rifampicin: Rifampicin is a high molecular weight drug primarily eliminated by the liver (75% via liver and 25% via kidneys). In patients with impaired renal function, the drug's elimination is decreased, leading to increased drug levels, which can cause toxicity. Therefore, dose adjustments are necessary in patients with impaired renal function, including the case of a creatinine clearance of 25 ml/min.

**Why Each Wrong Option is Incorrect:**

A. Ethambutol: As mentioned earlier, Ethambutol is primarily eliminated via the liver, not requiring dose adjustment in cases of impaired renal function.

B. Isoniazid: Similar to Ethambutol, Isoniazid clearance is mainly dependent on liver function, not renal function, hence no dose adjustment is necessary.

D. Streptomycin: As Streptomycin is primarily eliminated by the kidneys, dose adjustment is required in patients with impaired renal function.

**Clinical Pearl:**

In patients with chronic renal impairment, it is crucial to monitor drug levels and adjust doses accordingly to prevent toxicity and ensure optimal treatment outcomes. When adjusting doses in these patients, consider the drug's primary pathway of elimination (e.g., liver or kidney) and adjust accordingly. Antituberculosis drugs primarily eliminated by the kidneys require dose reductions, while those primarily eliminated via the liver do not.