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Cited by 83HIV/AIDS drug development and treatmentHIV/AIDS Research and InterventionsPharmacogenetics and Drug Metabolism

Lack of Pharmacokinetic Interaction between Rilpivirine and Integrase Inhibitors Dolutegravir and GSK1265744

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Ford, Susan L., Gould, Elizabeth, Chen, Shuguang, Margolis, David, Spreen, William, Crauwels, Herta, Piscitelli, Stephen·2013·Antimicrobial Agents and Chemotherapy
DOI 10.1128/aac.01235-13PMC PMC3811315
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Abstract

Dolutegravir (DTG) and GSK1265744 are HIV integrase inhibitors (INIs) in clinical development. The oral formulation of rilpivirine (RPV), a nonnucleoside reverse transcriptase inhibitor (NNRTI), has been approved for treatment-naive HIV infection. Long-acting depot injections of GSK1265744 and RPV are also being developed. This study evaluated the potential for drug interactions between RPV and these INIs. This phase 1, open-label, two-cohort, three-period, single-sequence crossover study evaluated oral coadministration of RPV with DTG or GSK1265744. Healthy subjects received DTG (50 mg every 24 h for 5 days) or GSK1265744 (30 mg every 24 h for 12 days) in period 1 followed by a washout, RPV (25 mg every 24 h for 11 or 12 days) in period 2, immediately followed by RPV (25 mg every 24 h) plus DTG (50 mg every 24 h) for 5 days or GSK1265744 (30 mg every 24 h) for 12 days in period 3. Steady-state pharmacokinetic (PK) parameters were estimated using noncompartmental analysis of data collected on the last day of each period. The combinations of RPV and DTG ( n = 16) and of RPV and GSK1265744 ( n = 11) were well tolerated; no grade 3 or 4 adverse events (AEs) or AE-related discontinuations were observed. The 90% confidence intervals for the area under the curve from time zero until the end of the dosage interval [AUC 0–τ ] and maximum concentration of drug in serum ( C max ) geometric mean ratios were within 0.8 to 1.25. Following administration of DTG + RPV, DTG and RPV C τ increased by 22% and 21%, respectively. Following administration of GSK1265744 + RPV, RPV C τ decreased 8%. DTG and GSK1265744 can be administered with RPV without dosage adjustment for either agent. These results support coadministration of RPV with DTG or GSK1265744 as either oral or long-acting depot injection regimens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01467531.)

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  • Half-lives of rilpivirine and cabotegravir in tablets have been estimated to be ~1-2 days.

    “In contrast, half-lives of rilpivirine and cabotegravir in tablets have been estimated to be ~1-2 days (refs. 91,92 ).”

    From Nanotechnology approaches for global infectious diseases (2021) · cites this paper as [92]

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Authors
Ford, S. L., Gould, E., Chen, S., Margolis, D., Spreen, W., Crauwels, H., & Piscitelli, S.
Affiliations
  • GlaxoSmithKline, Research Triangle Park, North Carolina, USA
  • Janssen (Belgium) (BE)
ORCID
Venue
Antimicrobial Agents and Chemotherapy
Publisher
American Society for Microbiology
Published
2013-11
Volume
57
Issue
11
Pages
5472-5477
ISSN
  • 0066-4804 (ISSN-L)
  • 1098-6596
DOI
10.1128/aac.01235-13
PMC
PMC3811315
OpenAlex
W2085167526
Cited by
83
References
13
Citations by year
2026: 1 · 2025: 2 · 2024: 6 · 2023: 5 · 2022: 3 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 7 · 2015: 13 · 2014: 11 · 2013: 5
FWCI
8.72
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Antimicrobial Agents and Chemotherapy (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • GlaxoSmithKline
  • ViiV Healthcare
  • Janssen Pharmaceuticals
Topics
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords
rilpivirine, dolutegravir, integrase inhibitors, drug-drug interactions, pharmacokinetics, HIV treatment, non-nucleoside reverse transcriptase inhibitors, HIV infection, dose adjustment, long-acting HIV therapy, tolerability, adverse events, AUC and Cmax
MeSH terms
Rilpivirine, Dolutegravir, Administration, Oral, Adult, Drug Administration Schedule, Drug Combinations, Drug Interactions, Female, Heterocyclic Compounds, 3-Ring, Humans, Male, Middle Aged, Nitriles, Oxazines, Piperazines, Pyridones, Pyrimidines, Cross-Over Studies, Reverse Transcriptase Inhibitors, HIV Integrase Inhibitors, Area Under Curve, Diketopiperazines, Healthy Volunteers

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