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.
Half-Life (t½)
PO: 3.5h
Dosing Guidelines
PO: Typical 150 (Range: 150–150)
Target Organ Systems
immune-hematologic
Interactions
Midazolam (major): CYP3A4 inhibition (mechanism-based). Mathias 2010 (PMID:20043009) verbatim: "GS-9350 potently inhibited midazolam apparent clearance (95% reduction), similar in effect to ritonavir 100 mg". Phase-1 single- + multiple-dose escalation, 50-400 mg cobicistat (GS-9350) + PO midazolam probe. CL ↓95% → AUC ratio 1/0.05 = 20×; Ki ≈ 1.5/19 = 0.079 µM. Cobicistat was DESIGNED as a CYP3A4 booster equivalent to RTV — the midazolam DDI is the design-intent test.