Daclatasvir
Daclatasvir. HCV NS5A inhibitor — first-in-class direct-acting antiviral targeting the viral phosphoprotein essential for HCV RNA replication… Oral half-life 13 h.
HCV NS5A inhibitor — first-in-class direct-acting antiviral targeting the viral phosphoprotein essential for HCV RNA replication complex assembly. Pan-genotypic at low concentrations. Was paired with sofosbuvir or asunaprevir in early DAA-era regimens; largely displaced by glecaprevir/pibrentasvir (Mavyret) and other co-formulated DAAs. CYP3A4 substrate; mild P-gp inhibitor. PK (Daklinza label, 60 mg PO qd SS): Cmax 1534 ng/mL, AUC 14122 ng·h/mL, Tmax ~2 h, t½ 12-15 h, F 67%, protein binding ~99%. High-fat meal ↓Cmax 28%, ↓AUC 23%. Steady state by day 4. CYP3A4 substrate + P-gp substrate; ritonavir / strong CYP3A4 inhibitors raise AUC ~3-fold.
PK: THE ABSORPTION RATE CONTRADICTED THE LABEL TEXT IN ITS OWN source_label STRING, which says peak concentrations occur "within 2 hours" while ka 0.7 predicted 3.98 h. Every other figure in that string verifies against the FDA label — "The absolute bioavailability of the tablet formulation is 67%", the 12-15 h half-life range — and the stored volume reproduces the European summary AUC to 0.7%, so only the rate moves. TWO TRAPS ARE RECORDED SO NOBODY "CORRECTS" THE VOLUME: the label separately states a steady-state volume of 47 L from an intravenous microdose, which is the most citable-looking number in the record and the WRONG one to store — it makes exposure worse — and it states a total clearance of 4.2 L/h which implies a volume near 79 L and an exposure 1.49x BELOW the same regulator own published figure. THE LABEL NUMBERS ARE MUTUALLY INCONSISTENT UNDER ONE COMPARTMENT: its volume and clearance together imply a 7.8 h half-life against its own stated 12-15. That is class 12 in the SOURCE, not in this record. Class 6 is acquitted — a human intravenous microdose exists. One prose defect: the mechanism string attributes its Cmax and AUC to the FDA label, but those figures are the European summary; the FDA label states no Cmax at all.
Pharmacokinetics
- Oral — t½ 13 h · F 67% · ka 1.82 h⁻¹ · Vd 53 L
Sources: PMID:29353349