Route of Administration for Captopril
Captopril is administered orally, not sublingually, as the standard and FDA-approved route of administration. 1
FDA-Approved Administration
The FDA drug label explicitly states that captopril is formulated for oral administration, with tablets designed to be swallowed 1. The pharmacokinetic profile is optimized for oral dosing, with approximately 75% absorption and peak blood levels occurring at about one hour after oral administration 1, 2.
Captopril should be given one hour before meals, as food in the gastrointestinal tract reduces absorption by 30-40%. 1
Evidence Against Sublingual Administration
Multiple high-quality studies demonstrate that sublingual administration offers no pharmacokinetic or clinical advantage over oral administration:
A randomized controlled trial in 40 hypertensive patients found no significant differences between oral and sublingual routes in the time course of blood pressure decrease, plasma renin activity increase, or ACE inhibition 3. The changes were superimposable regardless of administration route, directly refuting the hypothesis that sublingual captopril is absorbed more rapidly 3.
While some studies report faster initial blood pressure reduction with sublingual captopril in hypertensive crisis (10-30 minutes), this difference equalizes by 60 minutes, and the clinical significance is questionable 4, 5.
Guideline-Recommended Practice
Current clinical guidelines consistently recommend oral captopril administration across multiple clinical contexts:
For captopril renography in renovascular hypertension evaluation, guidelines specify oral administration of 25-50 mg captopril one hour before the procedure 6.
In hypertensive emergencies, the European Society of Cardiology position document recommends oral captopril (along with labetalol and nifedipine retard) for patients without acute hypertension-mediated organ damage, explicitly warning against short-acting formulations that cause rapid blood pressure falls 6.
Pediatric guidelines list captopril with oral dosing schedules (TID dosing) without any mention of sublingual administration 6.
Standard Oral Dosing
Initial dosing: 6.25 mg three times daily, with titration based on clinical response 6, 7
Maintenance dosing: 25-50 mg three times daily 6, 7
Target doses from clinical trials: Mean effective dose of approximately 127 mg/day (divided into three daily doses) 6, 7
Clinical Pitfalls to Avoid
Do not use sublingual captopril as standard practice. The sublingual route is not FDA-approved and offers no proven advantage over oral administration 1, 3.
Avoid administering captopril with food or antacids, as this significantly reduces bioavailability 1, 2.
Do not use captopril for rapid blood pressure reduction in hypertensive emergencies requiring immediate control—intravenous agents like labetalol or nicardipine are preferred 6.
Monitor renal function and potassium levels within 5-7 days after initiation, as captopril can cause hyperkalemia and renal dysfunction 6, 7.