Denosumab
Denosumab, a biologic. Fully human IgG2κ mAb binding RANKL (RANK ligand) → prevents RANKL engagement of RANK on osteoclast precursors →… Subcutaneous half-life 26 d.
Fully human IgG2κ mAb binding RANKL (RANK ligand) → prevents RANKL engagement of RANK on osteoclast precursors → blocks osteoclast formation, function, and survival → suppresses bone resorption. Functionally mimics endogenous osteoprotegerin. Rapid, reversible antiresorptive effect; discontinuation causes rebound resorption and vertebral fractures — strict continuity or transition to bisphosphonate required.
PK: ABSORPTION RATE AUTHORED FROM A VERBATIM PEAK TIME. This row carried no ka, so the solver substituted 1.0/h and the modelled peak landed at 6.8 h — for a slowly-absorbed subcutaneous product that is wrong by design, not by a little. Source: "median time to Cmax (tmax ) was 8 days (serum)" — a single 60 mg subcutaneous dose in healthy men. A stated MEDIAN, not a range interior. With the stored half-life fixing ke, Tmax solves uniquely for ka by inverting the model own definition, ln(ka/ke)/(ka-ke) = Tmax — ARITHMETIC, NOT AN ESTIMATE — giving 0.01449/h, which reproduces 192 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC entirely, so only the shape moves.
Pharmacokinetics
- Subcutaneous — t½ 26.0 d · F 62% · ka 0.01449 h⁻¹ · Vd 3.5 L
Sources: PMID:22087866, PMID:26447647