Etravirine
Etravirine. Second-generation NNRTI — flexible binding mode active against HIV-1 with first-generation NNRTI resistance mutations. Reserved for… Oral half-life 16 h.
Second-generation NNRTI — flexible binding mode active against HIV-1 with first-generation NNRTI resistance mutations. Reserved for treatment-experienced patients. CYP3A4 + CYP2C9 + CYP2C19 substrate + inducer.
PK: ITS SOURCE WAS A TELAPREVIR INTERACTION STUDY REPORTING ONLY PERCENTAGE CHANGES - "Telaprevir Cmin, Cmax, and AUC decreased 25%, 10%, and 16%" - and no half-life, volume, bioavailability or absorption rate for any drug. All four values were class 1 against it, and the antiviral over-representation in that class holds. F 0.30 IS DELETED RATHER THAN REPLACED because it is unknowable: no abstract states an absolute bioavailability for etravirine, both dedicated Clin Pharmacokinet reviews omit one, and there is no intravenous formulation. Everything moves to a population fit over 4728 concentrations in 817 adults: "Estimates of apparent total clearance (CL/F), apparent central volume of distribution (V c/F), first-order absorption rate constant (k a), and absorption lag-time were 41.7 L/h, 972 L, 1.16 h, and 1.32 h" - all apparent, so F is pinned to 1. THE HALF-LIFE IS DERIVED AND SAYS SO: 16.2 h is what that model own volume and clearance require, and it deliberately does NOT match the reviews 30-40 hour TERMINAL half-life, which a one-compartment model built on this volume cannot reproduce. Storing the literature 41 h beside V 972 would assert a clearance of 17.8 L/h against the measured 41.7, over-predicting exposure 2.3-fold; the old record under-predicted by 1.42. Exposure is the quantity the simulator exists to get right.
Pharmacokinetics
- Oral — t½ 16.2 h · F 100% · ka 1.16 h⁻¹ · Vd 972 L
Sources: PMID:25975423, PMID:27665573, PMID:19725591