ArticleClinical pharmacokinetics2010
Pharmacokinetics of multiple-dose darunavir in combination with low-dose ritonavir in individuals with mild-to-moderate hepatic impairment.
Article in Clinical pharmacokinetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 23 citations in OpenAlex.
- Pharmacokinetic profile and safety of adjusted doses of darunavir/ritonavir with rifampicin in people living with HIV.The Journal of antimicrobial chemotherapy · 2020Trial
- Pharmacokinetics and safety of boosted elvitegravir in subjects with hepatic impairment.Antimicrobial agents and chemotherapy · 2014Trial
- Drug-Drug Interactions Between HIV Antivirals and Concomitant Drugs in HIV Patients: What We Know and What We Need to Know.Pharmaceutics · 2024Review
- Pharmacokinetics under the COVID-19 storm.British journal of clinical pharmacology · 2023Article
- Successful Prediction of Human Fetal Exposure to P-Glycoprotein Substrate Drugs Using the Proteomics-Informed Relative Expression Factor Approach and PBPK Modeling and Simulation.Drug metabolism and disposition: the biological fate of chemicals · 2021Article
- Physiologically Based Pharmacokinetic Modeling for Predicting the Effect of Intrinsic and Extrinsic Factors on Darunavir or Lopinavir Exposure Coadministered With Ritonavir.Journal of clinical pharmacology · 2017Article
- Influence of Ethanol on Darunavir Hepatic Clearance and Intracellular PK/PD in HIV-Infected Monocytes, and CYP3A4-Darunavir Interactions Using Inhibition and in Silico Binding Studies.Pharmaceutical research · 2017Article
- Darunavir and ritonavir total and unbound plasmatic concentrations in HIV-HCV-coinfected patients with hepatic cirrhosis compared to those in HIV-monoinfected patients.Antimicrobial agents and chemotherapy · 2015Article
- Review
- Pharmacokinetic interaction between prasugrel and ritonavir in healthy volunteers.Basic & clinical pharmacology & toxicology · 2013Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectiveThe pharmacokinetics of some HIV protease inhibitors are altered in patients with hepatic impairment. The TMC114-C134 study assessed the pharmacokinetics and safety of darunavir/ritonavir 600 mg/100 mg twice daily in HIV-negative subjects with hepatic impairment (defined according to Child-Pugh classification A [mild] or B [moderate]) compared with matched, HIV-negative, healthy subjects.
methodsAll subjects received darunavir/ritonavir 600 mg/100 mg twice daily for 6 days with a morning dose on day 7. Pharmacokinetic profiles were obtained up to 72 hours post-dose for darunavir and 12 hours post-dose for ritonavir on day 7. Safety and tolerability were also assessed.
resultsDarunavir pharmacokinetics in subjects with mild (n = 8) and moderate (n = 8) hepatic impairment were comparable to those in matched healthy control subjects (n = 16). In those with mild hepatic impairment, the least square mean ratios relative to healthy subjects for darunavir exposure (the area under the plasma concentration-time curve from 0 to 12 hours) and for maximum and minimum plasma concentrations were 0.94 (90% CI 0.75, 1.17), 0.88 (90% CI 0.73, 1.07) and 0.83 (90% CI 0.63, 1.10), respectively. In those with moderate hepatic impairment, these values were 1.20 (90% CI 0.90, 1.60), 1.22 (90% CI 0.95, 1.56) and 1.27 (90% CI 0.87, 1.85), respectively. Ritonavir pharmacokinetics were comparable between healthy subjects and those with mild hepatic impairment, but mean exposure was 50% higher in subjects with moderate hepatic impairment. Darunavir/ritonavir was generally well tolerated, regardless of hepatic impairment. All adverse events were grade 1-2 in severity, except for a grade 3 increase in alanine aminotransferase reported in one subject with mild hepatic impairment. No adverse events led to discontinuation.
conclusionsThe results of this study show that the pharmacokinetics of darunavir/ritonavir 600 mg/100 mg are not affected by mild or moderate hepatic impairment. Therefore, it is recommended that dose adjustments of darunavir/ritonavir are not required in patients with mild or moderate hepatic impairment.
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