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

**Correct Answer:** D. Rifampicin

**Core Concept:**
In patients with chronic renal failure, dosage adjustments of anti-tuberculosis drugs are necessary to avoid toxic effects due to accumulation of drugs and their active metabolites. Renal clearance plays a crucial role in determining the elimination rate of these drugs.

**Why the Correct Answer is Right:**
Rifampicin is a bactericidal drug that has a high protein binding affinity and extensive tissue distribution. Its renal clearance accounts for only about 10% of its elimination, making it less dependent on renal function. As the patient has a creatinine clearance of 25 ml/min, the drug's elimination is primarily dependent on other non-renal mechanisms, thereby minimizing the risk of toxicity due to dose adjustment.

**Why Each Wrong Option is Incorrect:**

A. Streptomycin: Streptomycin is mainly eliminated through renal filtration, making dose adjustment necessary for patients with renal impairment.
B. Ethambutol: Ethambutol is predominantly eliminated by renal secretion, necessitating dose adjustment in renal dysfunction.
C. Isoniazid: Isoniazid is mainly eliminated through renal excretion, requiring dose adjustment in patients with impaired renal function.

**Clinical Pearl:**
In chronic renal failure patients with active pulmonary tuberculosis, the administration of drugs like Streptomycin, Ethambutol, and Isoniazid requires dose adjustment to prevent toxicity. However, Rifampicin, with its low renal clearance dependence, can be administered at standard doses without significant alterations in patients with creatinine clearance of 25 ml/min.

**Explanation:**
In a patient with chronic renal failure, it is essential to consider the pharmacokinetic properties of anti-tuberculosis drugs to avoid potential adverse effects due to drug accumulation. Rifampicin, with its low renal clearance dependence, can be given at normal doses in such patients without significant adjustments. On the other hand, drugs like Streptomycin, Ethambutol, and Isoniazid primarily rely on renal excretion for elimination, necessitating dose modification in patients with impaired renal function.