Everolimus

pharmacological · immune-hematologic · Oral

Everolimus. mTOR (mTORC1) inhibitor — binds FKBP12 → inhibits raptor-mTOR complex. Indications: HR+/HER2− breast cancer (with exemestane)… Oral half-life 18 h.

mTOR (mTORC1) inhibitor — binds FKBP12 → inhibits raptor-mTOR complex. Indications: HR+/HER2− breast cancer (with exemestane), advanced renal cell carcinoma, neuroendocrine tumors, TSC-associated SEGA and renal angiomyolipoma, immunosuppression in heart/kidney/liver transplant. CYP3A4 + P-gp substrate; therapeutic drug monitoring required at transplant doses (target trough 3-8 ng/mL). PK (Afinitor label, 10 mg PO qd oncology dose): Cmax 61.5 ng/mL (29.6% CV), AUC24 435 ng·h/mL (28.1% CV), Tmax 1-2 h, t½ 16-19 h, protein binding ~74%. Apparent CL/F 23 L/h, V/F 581 L. High-fat meal ↓AUC 22%, ↓Cmax 54%; light-fat meal ↓AUC 32%. CYP3A4 + P-gp substrate; therapeutic drug monitoring (target trough 3-8 ng/mL at transplant doses).

PK: MY MATRIX PRIOR IS REFUTED AND THE RECORD PICKED ONE MATRIX CONSISTENTLY. Both the apparent volume and the label clearance are WHOLE-BLOOD referenced and agree with each other, confirmed independently by a PLASMA-referenced analysis whose clearance is 8.6-fold larger — exactly this drug blood-to-plasma partition. Its internal arithmetic is among the best in the batch, reproducing the label exposure to a tenth of a percent. A LATENT TRAP IS DECLARED NOW RATHER THAN DISCOVERED LATER: the concentrations this record emits are WHOLE BLOOD, roughly eightfold above plasma, while the solver labels them plasma — so if anyone later authors a plasma free fraction or a plasma-referenced potency here, that becomes an eightfold live error overnight. THE FEASIBILITY FLOOR FAILS DECISIVELY AND UNFIXABLY: the label own peak, exposure and half-life sit three and a half fold below the minimum any one-compartment fit permits, so the record preserves exposure and pays on the peak, rendering it roughly four-fold low. THAT IS USER-VISIBLE AND NOT REPAIRABLE BY RE-TUNING ANY STORED FIELD. One reference supports nothing and CONTRADICTS: its only kinetic number is a half-life 1.7-fold longer than the stored one. It is KEPT because it supports the mechanism narrative, and its half-life is deliberately not adopted — at that value the one thing this record gets right would break.

Pharmacokinetics

Sources: PMID:18332470