ArticleEuropean journal of clinical pharmacology2014
Effects of enzyme inducers efavirenz and tipranavir/ritonavir on the pharmacokinetics of the HIV integrase inhibitor dolutegravir.
Article in European journal of clinical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01068925 (An Open-Label, Single Sequence, Three-Period Drug Interaction Study of GSK1349572 and Tipranavir/Ritonavir in Healthy Adult Subjects), which is not on this map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
An Open-Label, Single Sequence, Three-Period Drug Interaction Study of GSK1349572 and Tipranavir/Ritonavir in Healthy Adult Subjects (ING113096)
Who cites it
16 citing papers in PubMed, 39 citations in OpenAlex.
- Initial Supplementary Dose of Dolutegravir in Second-Line Antiretroviral Therapy: A Noncomparative, Double-Blind, Randomized Placebo-Controlled Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- Influence of Uridine Diphosphate Glucuronosyltransferase Family 1 Member A1 and Solute Carrier Organic Anion Transporter Family 1 Member B1 Polymorphisms and Efavirenz on Bilirubin Disposition in Healthy Volunteers.Drug metabolism and disposition: the biological fate of chemicals · 2020Trial
- Effect of rifampicin and efavirenz on moxifloxacin concentrations when co-administered in patients with drug-susceptible TB.The Journal of antimicrobial chemotherapy · 2017Trial
- Drug-Drug Interactions Between HIV Antivirals and Concomitant Drugs in HIV Patients: What We Know and What We Need to Know.Pharmaceutics · 2024Review
- Article
- 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
- Optimizing Moxifloxacin Dose in MDR-TB Participants with or without Efavirenz Coadministration Using Population Pharmacokinetic Modeling.Antimicrobial agents and chemotherapy · 2023Article
- PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5'-Diphospho-glucuronosyltransferase Substrates.Pharmaceutics · 2021Review
- Virologic efficacy of tenofovir, lamivudine and dolutegravir as second-line antiretroviral therapy in adults failing a tenofovir-based first-line regimen.AIDS (London, England) · 2021Article
- Implications of Efavirenz Pharmacogenetics When Switching From Efavirenz- to Dolutegravir-containing Antiretroviral Regimens.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2021Article
- AntiRetroviral Therapy In Second-line: investigating Tenofovir-lamivudine-dolutegravir (ARTIST): protocol for a randomised controlled trial.Wellcome open research · 2021Article
- Pharmacokinetic drug interactions of integrase strand transfer inhibitors.Current research in pharmacology and drug discovery · 2021Review
- Effect of carbamazepine on dolutegravir pharmacokinetics and dosing recommendation.European journal of clinical pharmacology · 2016Article
- Review
- Dolutegravir - a review of the pharmacology, efficacy, and safety in the treatment of HIV.Drug design, development and therapy · 2015Review
- Clinical effectiveness of dolutegravir in the treatment of HIV/AIDS.Infection and drug resistance · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDolutegravir (DTG) is an unboosted, integrase inhibitor for the treatment of HIV infection. Two studies evaluated the effects of efavirenz (EFV) and tipranavir/ritonavir (TPV/r) on DTG pharmacokinetics (PK) in healthy subjects.
methodsThe first study was an open-label crossover where 12 subjects received DTG 50 mg every 24 hours (q24h) for 5 days, followed by DTG 50 mg and EFV 600 mg q24h for 14 days. The second study was an open-label crossover where 18 subjects received DTG 50 mg q24h for 5 days followed by TPV/r 500/200 mg every 12 hours (q12h) for 7 days and then DTG 50 mg q24h and TPV/r 500/200 mg q12h for a further 5 days. Safety assessments and serial PK samples were collected. Non-compartmental PK analysis and geometric mean ratios and 90% confidence intervals were generated.
resultsThe combination of DTG with EFV or TPV/r was generally well tolerated. Four subjects discontinued the TPV/r study due to increases in alanine aminotransferase that were considered related to TPV/r. Co-administration with EFV resulted in decreases of 57, 39 and 75% in DTG AUC(0-τ), Cmax and Cτ, respectively. Co-administration with TPV/r resulted in decreases of 59, 46 and 76% in DTG AUC(0-τ), Cmax and Cτ, respectively.
conclusionsGiven the reductions in exposure and PK/pharmacodynamic relationships in phase II/III trials, DTG should be given at an increased dose of 50 mg twice daily when co-administered with EFV or TPV/r, and alternative regimens without inducers should be considered in integrase inhibitor-resistant patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.