Lopinavir
Lopinavir. HIV protease inhibitor — clinically available only as the Kaletra co-formulation with ritonavir (LPV/r 200/50 mg). Ritonavir component… Oral half-life 6 h.
HIV protease inhibitor — clinically available only as the Kaletra co-formulation with ritonavir (LPV/r 200/50 mg). Ritonavir component is sub-therapeutic for HIV but boosts lopinavir AUC ~80× via CYP3A4 inhibition. Largely displaced by integrase-inhibitor-based first-line regimens (DTG, BIC, RAL); retained for second-line use, pediatric HIV, and post-exposure prophylaxis in some settings. Investigated and rejected for COVID-19 (Recovery trial 2020 — no mortality benefit). Common AE: hyperlipidemia, insulin resistance, GI intolerance (worse than DRV/c). PK (Kaletra label, boosted 400/100 mg PO bid with RTV at SS): Cmax 9.8 ± 3.7 µg/mL, Cmin 5.5 ± 2.7 µg/mL, AUCtau (0-12) 92.6 ± 36.7 µg·h/mL. t½ ~6 h (boost makes effective t½ longer due to CYP3A4 inhibition). CL/F per 12-h interval ≈ 4.3 L/h, V/F ≈ 37 L.
PK: VERIFIED TO 6% ON EXPOSURE — DO NOT STRIP IT, AND DO NOT "FIX" THE VOLUME OR HALF-LIFE. Lopinavir has never been approved or marketed as a single agent anywhere; the fixed combination is the only product, so unlike elvitegravir there is no second prescribed state for the schema to be ambiguous between, and the only unboosted figure in the literature is explicitly a MODEL EXTRAPOLATION FROM BOOSTED DATA rather than an administered regimen. The stored clearance of 4.27 L/h sits against a verbatim "AUC(0-12) ... 99,599" at 400 mg twice daily, which is 4.02 — 6.4% high — and inside the 4.0 to 5.6 L/h real-world span. THE CONTRACT WARNING APPLIES DIRECTLY AND WAS HEEDED: the obvious replacement is a verbatim one-compartment pair from a study of the SAME SIXTEEN VOLUNTEERS as this record own reference, "the apparent volume of distribution and absorption rate constant were 55.3 liters ... and 0.57 h(-1)", but adopting its volume and half-life makes exposure 1.34x LOW where the current pair is 1.06x high. The individually unsourced volume and half-life have a RATIO — the only thing the solver uses for exposure — that is right. Only the absorption rate moves, and that is a provenance fix rather than an accuracy one. A milder ambiguity is noted: the dose block spans a twice-daily and a once-daily regimen whose interval half-lives differ, 7.15 against 4.88 hours.
Pharmacokinetics
- Oral — t½ 6 h · F 100% · ka 0.57 h⁻¹ · Vd 37 L
Sources: PMID:19043924, PMID:21172791, PMID:21422211