Losartan
Losartan. Angiotensin II AT1 receptor blocker — first ARB approved. Active E-3174 metabolite (via CYP2C9) drives most of the antihypertensive… Oral half-life 2.1 h.
Angiotensin II AT1 receptor blocker — first ARB approved. Active E-3174 metabolite (via CYP2C9) drives most of the antihypertensive effect. Renally protective in diabetic nephropathy. No bradykinin-cough; useful where ACEi caused intolerance.
PK: CLASS 12, AND THE CORRECT PAPER WAS NEVER CITED. Its source was an amlodipine interaction study containing none of the four stored values, and containing the number that convicts them: at that study own 100 mg dose the stored record predicts an AUC of 2801 against its observed 1241.50 ng.h/mL. Everything moves to the crossover that measured all of it in eighteen men — "the average plasma clearance of losartan was 610 ml/min, and the volume of distribution was 34 L ... Terminal half-life was 2.1 hours ... The oral bioavailability of losartan tablets was 33%". F 0.33 IS VERIFIED AND IS THE TABLET FIGURE, so the trap candesartan fell into is avoided here. But V 34 L is that study BI-EXPONENTIAL volume paired with its TERMINAL half-life, implying a clearance of 11.2 L/h against the same abstract 36.6 — 3.26x low. The terminal-phase volume the one-compartment model needs is 111 L, and both inputs are verbatim from the same sentence-pair. CLASS 6 IS ACQUITTED: losartan was dosed intravenously in that study, so this is a true volume and pairing it with F is correct. ka 2.5 is unsourced but reproduces the verbatim "peak concentrations ... reached in 1 hour", and is relabelled as derived rather than measured. THE ONSET FIGURE IN THE keo NOTE IS FROM RATS AND READS AS HUMAN. Its source says "In renal hypertensive rats ... a different onset of action (valsartan at 1 h, losartan between 2 h and 24 h)" — the species flag the occupancy notes already use is missing here. SEPARATELY, THE fu NOTE ARITHMETIC IS MUDDLED: it describes the metabolite as "0.4-0.5% free, seven times lower", but the sevenfold comparator is the naive-donor 0.2%, while 0.4-0.5% are the dosed-volunteer values and are only about three times lower. The conclusion is unaffected. AND THE MODEL UNDERSTATES BLOCKADE BY DESIGN: EXP3174 has an area under the curve "about four times that of losartan" at roughly nine times the potency, so a parent-only record cannot represent total AT1 engagement.
Pharmacokinetics
- Oral — t½ 2.1 h · F 33% · ka 2.249 h⁻¹ · Vd 111 L
Sources: PMID:8242249, PMID:1625192, PMID:7657853, PMID:8529329