Which of the following ACE inhibitors is a prodrug that requires hepatic metabolism to its active form?

Explanation

## ACE Inhibitors: Prodrug vs Active Forms **Key Point:** Enalapril is a prodrug that must be hydrolyzed by hepatic esterases to form enalaprilat, the active metabolite responsible for ACE inhibition. ### Classification of ACE Inhibitors | ACE Inhibitor | Type | Metabolism | Active Form | |---|---|---|---| | Enalapril | Prodrug | Hepatic esterase hydrolysis | Enalaprilat | | Ramipril | Prodrug | Hepatic metabolism | Ramiprilat | | Lisinopril | Active drug | Renal excretion unchanged | Lisinopril itself | | Perindopril | Prodrug | Hepatic hydrolysis | Perindoprilat | **High-Yield:** While enalapril, ramipril, and perindopril are all prodrugs, **enalapril** is the classic example tested in NEET PG because: - It is the most commonly prescribed ACE inhibitor in India - Its active metabolite (enalaprilat) can also be given intravenously in acute settings - The hepatic metabolism step is clinically significant in liver disease **Clinical Pearl:** Lisinopril is the only commonly used ACE inhibitor that is already in active form and does not require hepatic metabolism — it is excreted unchanged in urine, making it safer in hepatic impairment. **Mnemonic:** **"LERP"** — **L**isinopril (active), **E**nalapril (prodrug), **R**amipril (prodrug), **P**erindopril (prodrug). Lisinopril stands alone as the active agent. ### Clinical Implications - **Enalapril prodrug activation** takes 15–30 minutes orally; enalaprilat (IV form) acts within minutes - Hepatic disease may impair conversion of enalapril to enalaprilat, reducing efficacy - Ramipril and perindopril also require hepatic activation but are less frequently tested in isolation