Secukinumab
Secukinumab, a biologic. Fully human IgG1κ mAb selectively neutralising IL-17A (homodimer and IL-17A/F heterodimer) → blocks… Subcutaneous half-life 27 d.
Fully human IgG1κ mAb selectively neutralising IL-17A (homodimer and IL-17A/F heterodimer) → blocks keratinocyte, synoviocyte, and enthesial activation. First IL-17 pathway blocker approved. Highly effective for plaque psoriasis — PASI 90 rates ~70% by wk 16.
PK: volume and bioavailability from Bruin 2017 (PMID:28273356), a two-compartment population fit in moderate-to-severe plaque psoriasis, verbatim "central compartment volume, 3.61 L with IIV of 30% CV" and "The bioavailability of secukinumab after subcutaneous dosing was approximately 73%". The previous citation (PMID:25648267) is a genuine, correctly attributed paper about secukinumab whose abstract contains NO numeric pharmacokinetics whatsoever, yet carried all three stored values — a real-identifier, zero-content miscitation that a PMID-resolution gate cannot catch. HALF-LIFE PROVENANCE: the 648 h is retained but is LABEL-DERIVED, from the European summary of product characteristics, "The mean elimination half-life, as estimated from population pharmacokinetic analysis, was 27 days in plaque psoriasis patients"; no PubMed abstract states a numeric secukinumab half-life at all, which field-restricted sweeps of the whole database confirm. mw corrected from the generic 148000 to 151000 per the approval document. The stored 7 L is near the label's terminal-phase volume of 7.10-8.60 L, but that is a Vz rather than the central volume a model pairing a separate F needs, and it sits below even the stated floor. NOTE 3.61 L is a CENTRAL volume. 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: "The time to maximum serum concentration at steady state occurred approximately 6 days after dosing for both secukinumab 300 mg and secukinumab 150 mg". ITS OWN ABSTRACT ALSO STATES "an absorption rate of 0.18/day", WHICH DISAGREES 2.1-FOLD — that value implies a 12.6-day peak. It is one parameter of a two-compartment population fit, and lifting such a parameter into a one-compartment slot is the error documented on propofol's keo, so the OBSERVABLE is used. 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 0.0221/h, which reproduces 144 h on substitution. EXPOSURE IS UNCHANGED: the absorption rate cancels out of AUC entirely, so only the shape moves.
Pharmacokinetics
- Subcutaneous — t½ 27.0 d · F 73% · ka 0.0221 h⁻¹ · Vd 3.61 L
Sources: PMID:25648267, PMID:32973785, PMID:28273356