Guselkumab
Guselkumab, a biologic. Fully human IgG1λ mAb binding the p19 subunit of IL-23 → selectively blocks IL-23-driven Th17/Tc17 pathway. First… Subcutaneous half-life 15 d.
Fully human IgG1λ mAb binding the p19 subunit of IL-23 → selectively blocks IL-23-driven Th17/Tc17 pathway. First IL-23 p19-selective mAb approved. Strong durability — many patients maintain PASI 90 at wk 48+ on q8w dosing.
PK: Tran 2022 (PMID:35470450), a two-compartment population fit over 23,097 samples from 2623 healthy subjects and patients across nine phase 1-3 trials, verbatim "Clearance (CL), central and peripheral volume of distribution, intercompartmental flow, absorption rate constant and absolute bioavailability estimates were 0.255 L/d, 3.60 L, 1.78 L, 0.369 L/d, 0.313 d-1 and 49.2%, respectively, for a subject weighing 70 kg" and "Terminal half-life was estimated to be approximately 14.6 days" (350.4 h). Every value now comes from that one fit. The previous citation (PMID:29341192) states 18.1 days rather than the stored 17 days, gives an APPARENT volume of 13.5 L rather than 7 L, and — decisively — is a pool of three SUBCUTANEOUS-ONLY psoriasis trials, so the entire IV row had been sourced to a paper containing no IV data. The stored F of 0.49 was the right number attached to a model in which bioavailability is not even estimable. mw corrected from the generic 148000 to 147000 per the approval document. The absolute bioavailability is anchored by the first-in-human study's IV arm (PMID:27515978, 0.03-10 mg/kg IV in 47 healthy subjects). NOTE 3.60 L is a CENTRAL volume.
Pharmacokinetics
- Subcutaneous — t½ 14.6 d · F 49% · ka 0.01919 h⁻¹ · Vd 3.6 L
- IV — t½ 14.6 d · F 100% · Vd 3.6 L
Sources: PMID:29341192, PMID:34460338, PMID:35470450, PMID:27515978