Ramipril
Ramipril. ACE inhibitor prodrug — hepatic carboxylesterase converts to ramiprilat. HOPE trial (2000) demonstrated CV-event reduction in… Oral half-life 1.9 h.
ACE inhibitor prodrug — hepatic carboxylesterase converts to ramiprilat. HOPE trial (2000) demonstrated CV-event reduction in high-risk patients independent of BP lowering — drove modern preferred use of ACEi for cardioprotection.
PK: WRONG ANALYTE ON THE PARENT MASS. The stored molecular weight of 416.51 is the ETHYL ESTER; the active diacid ramiprilat is 388.46, an ester factor of 1.072. The stored 14 h was the DIACID accumulation value while the ester own half-life is about 1.9 h. F 0.55 was a RANGE MIDPOINT — "the bioavailability of oral ramipril seems to be in the range of 44-66%", and 44 plus 66 halved is 55 — while the same abstract gives both analyte-specific measurements: "The absolute bioavailability as judged by ramipril plasma AUC was 15%, by ramiprilat plasma AUC, 44%". For a record carrying the ester mass, 15% is the correct figure and is stored. THE LONG PUBLISHED HALF-LIVES ARE SATURABLE ENZYME BINDING: "The subsequent long terminal phase at low plasma ramiprilat concentrations represented slow dissociation of the ACE-inhibitor complex", and investigators computed exposure "excluding the component for saturable binding" to obtain usable kinetics. Effect inhibition declines with a half-life near 75 h, which is an EFFECT half-life and not storable as elimination. ka and V dropped as unsourced.
Pharmacokinetics
- Oral — t½ 1.9 h · F 15%
Sources: PMID:14755115, PMID:7768254, PMID:2533075