Dolutegravir
Dolutegravir. HIV integrase strand-transfer inhibitor (INSTI) — blocks integration of viral DNA into host genome. High barrier to resistance… Oral half-life 13 h.
HIV integrase strand-transfer inhibitor (INSTI) — blocks integration of viral DNA into host genome. High barrier to resistance; cornerstone of modern first-line ART. Modest UGT1A1 substrate; food doubles AUC.
PK: THE ELEVENTH ANTIVIRAL WHOSE CITATION SUPPORTS NONE OF ITS NUMBERS — and the arithmetic was sound anyway, so only the provenance and the absorption were wrong. Its old citation states one PK constant, "The half-life was approximately 15 h", which CONTRADICTED the value stored beside it. The absorption rate was the catalogue second-most-common value, shared with two dozen unrelated records, and implied a peak at 5.1 h against a published two to three. ALL FOUR REPLACEMENTS COME FROM A SINGLE SENTENCE OF ONE POPULATION ANALYSIS: "Population estimates for apparent clearance, apparent volume of distribution, absorption rate constant and absorption lag time were 0.901 l h(-1), 17.4 l, 2.24 h(-1), and 0.263 h" — with the lag, the apparent peak lands at 2.0 h. The half-life is the one the volume and clearance in that sentence jointly imply, so all four parameters now come from one fit of one cohort. BIOAVAILABILITY OF 1 IS VERIFIED, NOT ASSUMED: no intravenous dolutegravir exists and absolute bioavailability has never been established, so every published figure is already an apparent one and pinning F prevents dividing by it twice.
Pharmacokinetics
- Oral — t½ 13.4 h · F 100% · ka 2.24 h⁻¹ · Vd 17.4 L
Sources: PMID:19884365, PMID:25819132