Lovastatin
Lovastatin. First FDA-approved statin (1987). Lactone prodrug from Aspergillus terreus. CYP3A4 substrate — interaction-prone. Lower-potency than… Oral half-life 3.7 h.
First FDA-approved statin (1987). Lactone prodrug from Aspergillus terreus. CYP3A4 substrate — interaction-prone. Lower-potency than newer statins — largely displaced clinically.
ANALYTE: THE PARENT LACTONE — MY INFERENCE WAS REFUTED, AND THIS RECORD SHOULD NOT MATCH ITS SIBLING. The parent-ester tell does not apply here because lactone and acid have statistically indistinguishable half-lives in the same 12 volunteers: 3.7 +/- 2.5 h and 4.3 +/- 2.8 h. Nothing forces the record onto the acid. F 0.05 is verbatim, lovastatin-specific and describes the lactone, matching mw 404.55. A SEPARATE DEFECT CORRECTED: the stored 3 h was the top of a THREE-DRUG CLASS RANGE — "Lovastatin, pravastatin and simvastatin ... have elimination half-lives of 1-3 h" — and is replaced by the measured 3.7 h lactone value, so mass, bioavailability and half-life now all describe one species. PK: THE ANALYTE CHOICE IS CONFIRMED BY A TEST THE EARLIER PASS COULD NOT RUN, AND THE VOLUME IS THE SAME ORPHAN ALREADY DELETED NEXT DOOR. Its citation reports a full quartet for BOTH circulating species in the same twelve volunteers, so the feasibility bound can be applied to each: the LACTONE arm needs an exposure-to-peak ratio of at least e times its peak time, 4.62 h, and observes 5.22 — REPRESENTABLE; the ACID arm needs 11.14 and observes 5.90 — UNFITTABLE AT ANY VOLUME, ANY BIOAVAILABILITY AND ANY ABSORPTION RATE. THE RECORD IS ON THE ONLY SPECIES THIS MODEL CAN CARRY, and the simvastatin analogy does not transfer. The volume was unsupported and is THE IDENTICAL ORPHAN NUMBER ALREADY REMOVED FROM SIMVASTATIN, whose note records that no human volume exists; here it over-predicted exposure 1.79-fold against the cited paper own verbatim figure. The replacement is DERIVED, NOT VERBATIM — the value that reproduces that exposure at the stored bioavailability and half-life — and is stored rather than deleted because the silent default is further from the truth than a declared derivation. A NEAR-MISS IS RECORDED AND DELIBERATELY NOT ACTED ON: the lactone ratio sits about two percent below the theoretical floor, which against a published spread of plus or minus 79 percent is noise.
Pharmacokinetics
- Oral — t½ 3.7 h · F 5% · Vd 251 L
Sources: PMID:15660968, PMID:11868800