Bioequivalence of a Fixed-Dose Combination Tablet of the Complete Two-Drug Regimen of Dolutegravir and Rilpivirine for Treatment of HIV-1 Infection

Abstract

A complete 2-drug regimen of dolutegravir at 50 mg and rilpivirine at 25 mg was approved to treat HIV-1 infection in virologically suppressed patients after demonstrating acceptable efficacy and tolerability. This study investigated the bioequivalence and pharmacokinetics of the fixed-dose combination tablet compared with those of separate tablets.

Dolutegravir-Rilpivirine, Dual Antiretroviral Therapy for the Treatment of HIV-1 Infection

“…A fixed-dose combination (FDC) tablet of DTG-RPV achieved similar maximum concentration ( C max ), steady-state concentration ( C ss ), and area under the concentration-time curve (AUC) when compared with the administration of DTG and RPV as separate tablets as well as the FDC DTG/abacavir/lamivudine and RPV/emtricitabine/tenofovir disoproxil fumarate, respectively (Table 1). 12-14…”

“…A fixed-dose combination (FDC) tablet of DTG-RPV achieved similar maximum concentration (C max ), steadystate concentration (C ss ), and area under the concentrationtime curve (AUC) when compared with the administration of DTG and RPV as separate tablets as well as the FDC DTG/abacavir/lamivudine and RPV/emtricitabine/tenofovir disoproxil fumarate, respectively (Table 1). [12][13][14] To achieve consistent drug levels of RPV, DTG-RPV should be administered with a high-fat meal containing at least 400 calories and 13 g of fat. 13 Both DTG and RPV are ~99% protein bound, with the primary protein being albumin.…”

“…Less than 1% of both DTG and RPV are excreted unchanged in the urine, whereas 53% of DTG and 25% of RPV are excreted in the feces unchanged. 12…”

“…Steady-State Pharmacokinetic Properties [12][13][14]. FDC, fixed-dose combination; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate.…”

<p>The Effect of Moderate- and High-Fat Meals on the Bioavailability of Dolutegravir/Rilpivirine Fixed-Dose Combination Tablet</p>

“…The approvals were based on the results of two Phase 3 trials (SWORD 1 and 2) which demonstrated non-inferior efficacy and safety of DTG + RPV once daily with a meal when compared to current 3-drug antiretroviral therapy, 1 and a pivotal bioequivalence (BE) study in fed condition which demonstrated that a fixed-dose combination tablet (DTG/RPV) was bioequivalent to the single entity tablets. 2 During the course of drug development, a relative bioavailability (BA) study was conducted to evaluate the pharmacokinetics of multiple experimental fixeddose combination (FDC) formulations in both the fasted and fed states in order to select the best FDC tablet formulation and to estimate food effect. 3 This communication will report the effect of food (moderate-and high-fat/calorie meals) on the pharmacokinetics of one of the DTG/RPV fixed-dose combination tablets: Formulation AM.…”