Captopril vs Lisinopril

Overview

Captopril was the first ACE inhibitor approved for clinical use (1981) and remains pharmacologically important but is now rarely used as a first-line agent due to its thrice-daily dosing and unique side effects. Lisinopril is once-daily and better tolerated.

Mechanism of Action

Both inhibit ACE and are active as administered (neither is a prodrug). Captopril contains a sulfhydryl group critical for ACE binding; lisinopril is a lysine analog without a sulfhydryl group.

Pharmacokinetics

Captopril: bioavailability ~65–70%, half-life ~2 h, requires dosing 2–3×/day, renally eliminated. Food reduces captopril absorption by ~35–40%. Lisinopril: bioavailability ~25%, half-life ~12 h, once-daily dosing, renally excreted unchanged.

Sulfhydryl-Related Side Effects

Captopril's unique sulfhydryl group is linked to rash, dysgeusia (taste disturbance), and rarely proteinuria. These adverse effects are absent with lisinopril and other non-sulfhydryl ACEi. Both share the class-wide cough (bradykinin-mediated) and angioedema risks.

Clinical Evidence

SAVE trial (captopril post-MI LV dysfunction) was landmark. However, lisinopril (ATLAS, GISSI-3) has comparable evidence with superior dosing convenience.

Key Takeaways

• Captopril: historical first ACEi, active drug, sulfhydryl side effects (dysgeusia, rash), 3×/day
• Lisinopril: once-daily, better tolerated, no sulfhydryl issues
• Both renally cleared; dose adjust in CKD