ArticleClinical infectious diseases : an official publication of the Infectious Diseases Society of America2023
Management of Drug-Drug Interactions Between Long-Acting Cabotegravir and Rilpivirine and Comedications With Inducing Properties: A Modeling Study.
Article in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Long-Acting Injectable Antiretroviral Therapies for HIV Treatment and Prevention: Clinical Pharmacology, Recent Advances and Future Opportunities.Journal of clinical pharmacology · 2026Review
- Interactions between long-acting antiretrovirals and opioids: a call for clinical awareness.Clinical microbiology reviews · 2026Review
- Long-acting Cabotegravir/Rilpivirine for Treatment of HIV During Pregnancy: A Case Series.Open forum infectious diseases · 2025Article
- The Meandrous Route of Rilpivirine in the Search for the Miraculous Drug to Treat HIV Infections.Viruses · 2025Article
- Sustained HIV Viral Suppression 18 Months After the Last Dose of Long-acting Cabotegravir/Rilpivirine: A Case Report.Open forum infectious diseases · 2025Article
- Long-Acting Injectable Antiretroviral Therapy for Treatment of Human Immunodeficiency Virus: A Review.Current HIV/AIDS reports · 2025Review
- Application of Physiologically Based Pharmacokinetic Modeling in the Research of Anti-HIV Drugs.Current drug metabolism · 2025Review
- Effect of Obesity on the Exposure of Long-acting Cabotegravir and Rilpivirine: A Modeling Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024Article
- Pharmacokinetics-Pharmacodynamics Modeling for Evaluating Drug-Drug Interactions in Polypharmacy: Development and Challenges.Clinical pharmacokinetics · 2024Review
- Physiologically based Pharmacokinetic Model Validated to Enable Predictions Of Multiple Drugs in a Long-acting Drug-combination Nano-Particles (DcNP): Confirmation with 3 HIV Drugs, Lopinavir, Ritonavir, and Tenofovir in DcNP Products.Journal of pharmaceutical sciences · 2024Article
- Development of a physiologically-based pharmacokinetic model to simulate the pharmacokinetics of intramuscular antiretroviral drugs.CPT: pharmacometrics & systems pharmacology · 2024Article
- Role of Modeling and Simulation in Preclinical and Clinical Long-Acting Injectable Drug Development.The AAPS journal · 2023Review
- Management of Drug Interactions with Inducers: Onset and Disappearance of Induction on Cytochrome P450 3A4 and Uridine Diphosphate Glucuronosyltransferase 1A1 Substrates.European journal of drug metabolism and pharmacokinetics · 2023Article
- Pharmacological outlook of Lenacapavir: a novel first-in-class Long-Acting HIV-1 Capsid Inhibitor.Le infezioni in medicina · 2023Review
- Drug-drug interactions between COVID-19 therapeutics and antiretroviral treatment: the evidence to date.Expert opinion on drug metabolism & toxicologyReview
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Authors and funding
5 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundLong-acting (LA) intramuscular cabotegravir and rilpivirine are prone to drug-drug interactions (DDI). However, given the long dosing interval, the conduct of clinical DDIs studies with LA antiretrovirals is challenging. We performed virtual clinical DDI studies using physiologically based pharmacokinetic (PBPK) modeling to provide recommendations for the management of DDIs with strong or moderate inducers such as rifampicin or rifabutin.
methodsEach DDI scenario included a cohort of virtual individuals (50% female) between 20 and 50 years of age with a body mass index of 18-30 kg/m2. Cabotegravir and rilpivirine were given alone and in combination with rifampicin or rifabutin. The predictive performance of the PBPK model to simulate cabotegravir and rilpivirine pharmacokinetics after oral and intramuscular administration and to reproduce DDIs with rifampicin and rifabutin was first verified against available observed clinical data. The verified model was subsequently used to simulate unstudied DDI scenarios.
resultsAt steady state, the strong inducer rifampicin was predicted to decrease the area under the curve (AUC) of LA cabotegravir by 61% and rilpivirine by 38%. An increase in the dosing frequency did not overcome the DDI with rifampicin. The moderate inducer rifabutin was predicted to reduce the AUC of LA cabotegravir by 16% and rilpivirine by 18%. The DDI with rifabutin can be overcome by administering LA cabotegravir/rilpivirine monthly together with a daily oral rilpivirine dose of 25 mg.
conclusionsLA cabotegravir/rilpivirine should be avoided with strong inducers but coadministration with moderate inducers is possible by adding oral rilpivirine daily dosing to the monthly injection.
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