Pibrentasvir Intermediate 1007881-21-1

China [CN]

I. Basic Information

Generic Name: Pibrentasvir

Development Code: ABT-530

CAS Number: 1353900-92-1

Molecular Formula: C₅₇H₆₅F₅N₁₀O₈

Molecular Weight: 1113.18

Original Developer: AbbVie

Clinical Form: Fixed-dose combination (GLE 100 mg + PIB 40 mg/tablet)

II. Mechanism of Action

Target: HCV NS5A protein (a core regulatory factor in viral replication, assembly, and release)

Mechanism: Potently inhibits NS5A function, blocking viral RNA replication, viral particle assembly, and release.

Pangenotypic Activity: Potent picomolar (pM) inhibition against HCV genotypes 1–6 (EC₅₀: 1.4–5.0 pM)

Resistance Profile: Maintains activity against common NS5A resistance mutations (e.g., Y93H, Q30D), significantly reducing the risk of resistance.

Combination Synergy: Used in combination with glecaprevir (an NS3/4A inhibitor), providing dual-target blockade for pangenotypic activity, high cure rates, and short treatment duration.

III. Core Indications (GLE/PIB Combination)

For patients aged 3 years and older with HCV genotypes 1–6, without cirrhosis or with compensated cirrhosis (Child-Pugh A):

Treatment-naïve patients: All genotypes (1–6), 8-week treatment course, SVR₁₂ ≈ 95%–100%

Treatment-experienced patients: Genotype 1, previously treated only with NS5A inhibitors or NS3/4A inhibitors (not both simultaneously), 16-week treatment course

Special populations: Renal impairment/dialysis, children (3–17 years), HIV/HCV co-infection, acute HCV

IV. Pharmacokinetics (PIB)

Absorption: Increased bioavailability when taken with food

Protein Binding: >99.9%

Metabolism: Primarily via non-CYP pathways Metabolic pathway (low risk of drug interactions)

Half-life: approximately 13 hours

Excretion: 96.6% in feces, <1% in urine (no dose adjustment needed for renal impairment)

V. Adverse Reactions (Combination Therapy)

Common (≥5%): headache, fatigue, nausea, diarrhea, pruritus

Serious: elevated liver enzymes (ALT/AST), elevated bilirubin; contraindicated in decompensated cirrhosis

Contraindications: Child-Pugh B/C cirrhosis, concomitant use with atazanavir/rifampicin, allergy

VI. Drug Interactions (Key)