Cobicistat
Cobicistat. Pharmacological enhancer / "booster" with no intrinsic anti-HIV activity. Mechanism-based inhibitor of human CYP3A4 (and CYP2D6 to a… Oral half-life 3.5 h.
Pharmacological enhancer / "booster" with no intrinsic anti-HIV activity. Mechanism-based inhibitor of human CYP3A4 (and CYP2D6 to a lesser extent), designed specifically to replace ritonavir for boosting CYP3A4-metabolized antiretrovirals — elvitegravir (Stribild/Genvoya), atazanavir (Evotaz), darunavir (Prezista with cobi / Symtuza). Inhibition of intestinal + hepatic CYP3A4 first-pass extends victim t½ and raises AUC ~20× for midazolam. Inhibits OATP1B1/B3 and P-gp at clinically relevant concentrations. Causes mild creatinine rise (~0.1-0.2 mg/dL) via inhibition of MATE1 / OCT2 tubular secretion — not true GFR decline. PK (Tybost prescribing info rev 6/2025; SS 150 mg PO qd): Cmax 0.99 ± 0.3 µg/mL, AUCtau 7.6 ± 3.7 µg·h/mL, Tmax ~3.5 h, t½ 3-4 h, protein binding 97-98%. CL/F ≈ 19.7 L/h, V/F ≈ 99.5 L.
PK PROVENANCE, moved here from source_label when that field was shortened to a citation that names the label revision: Derived from FDA label Tybost (cobicistat) 150 mg PO qd exposure figures: the label states Cmax, AUCtau, Ctau and t½ ~3–4 h but NO volume and NO clearance. V/F 99.5 L is back-derived as (dose/AUC)·(t½/ln2); ka 0.7 is a catalog default. PK: THE MOST INTERNALLY COHERENT RECORD IN ITS GROUP, WITH TWO PROVENANCE DEFECTS AND NO ARITHMETIC ONE. Its exposure figures reproduce each other exactly and it passes the feasibility floor. But its label citation presented as a label figure a volume THE LABEL DOES NOT CONTAIN — that document gives peak, trough and exposure and NEITHER A VOLUME NOR A CLEARANCE — so the number is a legitimate back-derivation wearing the wrong clothes, and the attribution is rewritten to say so. THE INTERACTION CONSTANT IS DELETED RATHER THAN REPAIRED: it was computed from an exposure ratio, its note says so openly, and storing a computed affinity as a measured one is exactly what the verbatim rule forbids. TWO FURTHER PROBLEMS MADE REPAIR POINTLESS: the inhibitor concentration in that derivation is unsourced and disagrees with the label own peak, and the derivation inverts a COMPETITIVE relationship while the edge is flagged mechanism-based, so the two halves are inconsistent with each other. THE VERBATIM EFFECT IS KEPT IN PROSE — "GS-9350 potently inhibited midazolam apparent clearance (95% reduction), similar in effect to ritonavir 100 mg" — which is the honest quantity. AND A PERPETRATOR QUESTION IS ANSWERED PREEMPTIVELY: adding boosting edges here would DOUBLE-COUNT, because lopinavir and darunavir already declare in their own source labels that their apparent parameters are the ritonavir-boosted ones.
Pharmacokinetics
- Oral — t½ 3.5 h · F 100% · ka 0.3961 h⁻¹ · Vd 99.5 L
Related compounds
- Midazolam — major
Sources: PMID:20043009