Simvastatin
Simvastatin. Lactone prodrug of simvastatin acid. Lipophilic — greater CNS penetration than rosuvastatin. CYP3A4 substrate — heavy interaction… Oral half-life 5.9 h.
Lactone prodrug of simvastatin acid. Lipophilic — greater CNS penetration than rosuvastatin. CYP3A4 substrate — heavy interaction profile. Peak endogenous cholesterol synthesis occurs nocturnally → evening dosing for short-t½ statins.
PK models SIMVASTATIN ACID, the active species — the parent is an inactive lactone prodrug, and its own citation says so: "simvastatin is not active, while its metabolites are". Half-life 5.9 h is Ucar 2004 (PMID:14691614), 12 healthy volunteers, 80 mg, verbatim "half-life of simvastatin acid was shortened from 5.9+/-0.3 h". THE STORED 3 h WAS NOT A HALF-LIFE AT ALL: it is the midpoint of "peak inhibition of HMG-CoA reductase activity occurs within 2 to 4 hours", a pharmacodynamic time to peak effect. F corrected 0.05 -> 0.07, the figure its own citation states: "only 7% of the dose reaches the general circulation intact" — which describes the parent lactone. V 140 L dropped: no human volume exists, and at 5-7% bioavailability any apparent volume paired with F would double-count a near-total first-pass extraction. A RECORD BATCH C1 ALREADY "RESOLVED", REOPENED — AND THE VERIFICATION AGENT FOUND IT, NOT THE PASS THAT CREATED IT. C1 labelled this active-metabolite on the strength of its own note, but that same note concedes the stored bioavailability of 0.07 "describes the parent lactone" ("only 7% of the dose reaches the general circulation intact"). So the row paired an ACID half-life with a LACTONE bioavailability under an active-metabolite label — the exact chimera this pass exists to eliminate. F is now pinned to 1 so the row describes one species throughout, and the measured 7% systemic availability of the PARENT is recorded here instead. Contrast lovastatin, which is genuinely parent: the two statin records legitimately differ. MASS: the stored molecular weight described the PARENT while pk_analyte declares the metabolite, so the one field that must name a single species named the wrong one. LATENT RATHER THAN LIVE — this record carries no occupancy rows and is no other record interaction perpetrator — but it is one authored edge away from being live, because both consumers of the field (the micromolar-to-mass conversion for a kinetics edge, and the affinity the app renders from a stored occupancy concentration) want the species that actually circulates, which is the species pk[] already describes.
Pharmacokinetics
- Oral — t½ 5.9 h · F 100%
Related compounds
- Gemfibrozil — major
Sources: PMID:8343198, PMID:14691614