Fosinopril
Fosinopril. ACE inhibitor prodrug — phosphinic acid moiety distinguishes it. Dual hepatic + renal clearance (only ACEi with this — others are… Oral half-life 17 h.
ACE inhibitor prodrug — phosphinic acid moiety distinguishes it. Dual hepatic + renal clearance (only ACEi with this — others are predominantly renal) → no dose adjustment in mild renal impairment.
ANALYTE: FOSINOPRILAT, and the strongest analyte case of the nine — its cited study sampled "for fosinoprilat concentrations over 48 hours" on BOTH the oral and intravenous arms, so the diacid is the only species measured anywhere in it. AND A NEW DEFECT: V 26 L CONTRADICTS THAT SAME CITATION, which states "a Vss of 5,850 +/- 2,780 mL" — 5.85 L, a 4.4-fold error, with 26 appearing nowhere. The stored 12 h was likewise in neither row; the paper gives 17.4 h oral and 13.0 h intravenous, and the oral value is carried. ka 0.4 is unstated and dropped. mw 563.66 is the parent phosphinate ester. PK: THIS REVERSES ONE OF MY OWN EARLIER FIXES, AND THE LESSON IS THAT VERBATIM IS NOT SUFFICIENT. An earlier pass replaced a volume of 26 L with the verbatim 5.85 from "a Vss of 5,850 +/- 2,780 mL", calling 26 a 4.4-fold error that appeared nowhere. THE VERBATIM NUMBER IS THE WRONG KIND OF VOLUME: that abstract fits a multi-compartment intravenous profile, and the one-compartment surrogate is the terminal volume, not the steady-state one. THE RECORD HAS BEEN OVER-PREDICTING EXPOSURE 5.8x EVER SINCE, against that same paper own verbatim oral exposure — where the deleted 26 was 1.30x. Three independent routes converge on twenty to twenty-seven litres and the deleted value sat inside that band. The replacement is the paper own verbatim clearance divided by the rate its own verbatim half-life implies. A SECOND FINDING IS RECORDED RATHER THAN ACTED ON: the stored bioavailability is verbatim but is a MOLAR figure, and the solver multiplies dose by it as MASS — with a prodrug dose and a metabolite analyte the correct mass factor is nearer 0.157. AND THE FEASIBILITY BOUND FAILS IN ITS STRONGEST FORM: the published exposure-to-peak ratio of 8.92 h sits below e times the peak time, 10.87 h, which no half-life whatsoever can satisfy — the only escape is an absorption lag, physically sensible for an ester requiring hydrolysis. MASS: the stored weight was the prodrug while the declared analyte is fosinoprilat — 29.4 percent high, second only to tenofovir-disoproxil in this series. Inert today (no occupancy rows, no interaction edge), but it is the same molar/mass confusion that makes the stored bioavailability wrong as a mass factor.
Pharmacokinetics
- Oral — t½ 17.4 h · F 22% · Vd 27.3 L
Sources: PMID:11563407, PMID:9549638