Comparative Pharmacology
Head-to-head clinical analysis: DOLUTEGRAVIR EMTRICITABINE TENOFOVIR ALAFENAMIDE versus DOLUTEGRAVIR LAMIVUDINE AND TENOFOVIR DISOPROXIL FUMARATE.
Peer-Reviewed Evidence
Head-to-head clinical analysis: DOLUTEGRAVIR EMTRICITABINE TENOFOVIR ALAFENAMIDE versus DOLUTEGRAVIR LAMIVUDINE AND TENOFOVIR DISOPROXIL FUMARATE.
DOLUTEGRAVIR; EMTRICITABINE; TENOFOVIR ALAFENAMIDE vs DOLUTEGRAVIR, LAMIVUDINE AND TENOFOVIR DISOPROXIL FUMARATE
Comparing the clinical profiles, pharmacokinetic behaviors, and safety indices of these two therapeutic agents.
Dolutegravir is an HIV-1 integrase strand transfer inhibitor (INSTI) that blocks the integration of HIV-1 DNA into host genomic DNA. Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) that inhibits HIV-1 reverse transcriptase by competing with the natural substrate and causing chain termination. Tenofovir alafenamide is an NRTI that is converted to tenofovir, which inhibits HIV-1 reverse transcriptase after phosphorylation.
Dolutegravir is an integrase strand transfer inhibitor that blocks HIV-1 integration into host DNA. Lamivudine and tenofovir disoproxil fumarate are nucleoside reverse transcriptase inhibitors that inhibit HIV-1 reverse transcriptase via DNA chain termination.
One tablet (dolutegravir 50 mg; emtricitabine 200 mg; tenofovir alafenamide 25 mg) orally once daily.
One tablet (50 mg dolutegravir/300 mg lamivudine/300 mg tenofovir disoproxil fumarate) orally once daily
None Documented
None Documented
Dolutegravir: ~14 hours (single dose), ~12 hours (steady state). Emtricitabine: ~10 hours. Tenofovir alafenamide: ~0.5 hours; active metabolite tenofovir diphosphate intracellular half-life ~150-180 hours.
Dolutegravir: ~14 hours (terminal), supports once-daily dosing with moderate PK variability. Lamivudine: ~18-22 hours (terminal), allows once-daily dosing; intracellular active metabolite (lamivudine triphosphate) has much longer half-life (~22-27 hours). Tenofovir: ~17 hours (terminal), increased to ~32 hours in intracellular diphosphate form; supports once-daily dosing.
Dolutegravir: 64% fecal (unchanged), 31% renal (parent and metabolites). Emtricitabine: 86% renal (unchanged). Tenofovir alafenamide: ~80% renal (as tenofovir); <1% fecal.
Dolutegravir: ~64% feces (primarily as parent drug), ~32% urine (parent drug and glucuronide conjugate). Lamivudine: ~70% urine as unchanged drug (renal tubular secretion). Tenofovir disoproxil fumarate (TDF): Pro-drug; tenofovir is renally excreted ~70-80% unchanged (glomerular filtration and tubular secretion).
Category A/B
Category A/B
NRTI
NRTI