The effect of antacid and mineral supplements on bictegravir pharmacokinetics: results from a Phase 1, open-label, drug-drug interaction study
Abstract
The mechanism of action of integrase strand transfer inhibitors involves binding to magnesium ions in the active site of the HIV integrase enzyme, making them susceptible to chelation-type drug-drug interactions with metal cation-containing medications. This study evaluated the potential of metal cation-containing antacids and mineral supplements to impact bictegravir (BIC) exposure and assessed alternative approaches for combined use. This was an open-label, single-dose, Phase 1 study in adult participants without HIV. The pharmacokinetics and safety of BIC (administered as part of a single-tablet combination with emtricitabine [F] and tenofovir alafenamide [TAF; B/F/TAF]) were assessed when co-administered with maximum-strength aluminum/magnesium-containing antacid (referred to as "aluminum/magnesium-containing antacid"), calcium carbonate, or ferrous fumarate under fasted and fed conditions, and administered 2 hours before or after the antacid. Pharmacokinetic parameters were compared using analysis of variance to calculate geometric least-squares mean ratios and 90% confidence intervals. Forty-two participants were enrolled. BIC exposure (area under the plasma concentration-time curve extrapolated to infinity) was reduced by 79%, 33%, and 63%, respectively, when co-administered with aluminum/magnesium-containing antacid, calcium carbonate, and ferrous fumarate under fasted conditions. Co-administration of B/F/TAF with calcium carbonate or ferrous fumarate with a meal and…
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Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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