A patient with reduced renal function receives Drug Z with LED = 10 mg and LTD = 30 mg (TI = 3) and Drug W with LED = 10 mg and LTD = 1000 mg (TI = 100). The patient's impaired renal clearance is expected to double systemic exposure to either drug. Which drug poses a greater risk after renal impairment and why?

• A. Both drugs are equally dangerous after renal impairment since doubling systemic exposure always results in toxicity for any drug unless its TI is exactly 1.
• B. Drug W is riskier because the large LTD implies more accumulation potential and therefore higher absolute toxicity risk after renal impairment, regardless of TI.
• C. Neither drug is affected by renal impairment because TI is a static property that does not change with pharmacokinetic alterations, so risk remains the same.
• D. Drug Z poses the greater risk because a doubling of systemic exposure would move a typical therapeutic dose much closer to the LTD (TI = 3), increasing the likelihood of toxicity; Drug W's large TI provides a greater buffer against exposure increases.

Answer: (D)