Trial reportAntimicrobial agents and chemotherapy2000
Single-dose pharmacokinetics of amprenavir, a human immunodeficiency virus type 1 protease inhibitor, in subjects with normal or impaired hepatic function.
Trial report in Antimicrobial agents and chemotherapy, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 77 citations in OpenAlex.
- Clinical pharmacokinetics of nelfinavir and its metabolite M8 in human immunodeficiency virus (HIV)-positive and HIV-hepatitis C virus-coinfected subjects.Antimicrobial agents and chemotherapy · 2005Trial
- Recent Updates on Viral Oncogenesis: Available Preventive and Therapeutic Entities.Molecular pharmaceutics · 2023Review
- The Potential of Long-Acting, Tissue-Targeted Synthetic Nanotherapy for Delivery of Antiviral Therapy Against HIV Infection.Viruses · 2020Review
- Recent developments of nanotherapeutics for targeted and long-acting, combination HIV chemotherapy.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2019Review
- A Prediction Model of Drug Exposure in Cirrhotic Patients According to Child-Pugh Classification.Clinical pharmacokinetics · 2015Article
- Anti-HCV antibody among newly diagnosed HIV patients in Ughelli, a suburban area of Delta State Nigeria.African health sciences · 2015Article
- Relevance of Liver Failure for Anti-Infective Agents: From Pharmacokinetic Alterations to Dosage Adjustments.Therapeutic advances in infectious disease · 2014Article
- CYP3A activity in severe liver cirrhosis correlates with Child-Pugh and model for end-stage liver disease (MELD) scores.British journal of clinical pharmacology · 2014Article
- Drug disposition in pathophysiological conditions.Current drug metabolism · 2012Review
- Antiretroviral drug interactions: overview of interactions involving new and investigational agents and the role of therapeutic drug monitoring for management.Pharmaceutics · 2011Article
- Pharmacokinetics of dl-praeruptorin A after single-dose intravenous administration to rats with liver cirrhosis.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2011Article
- Pharmacokinetics of multiple-dose darunavir in combination with low-dose ritonavir in individuals with mild-to-moderate hepatic impairment.Clinical pharmacokinetics · 2010Article
- Pharmacokinetics of fosamprenavir plus ritonavir in human immunodeficiency virus type 1-infected adult subjects with hepatic impairment.Antimicrobial agents and chemotherapy · 2009Article
- An overview of HIV and chronic viral hepatitis co-infection.Digestive diseases and sciences · 2008Review
- Antiretroviral therapy : pharmacokinetic considerations in patients with renal or hepatic impairment.Clinical pharmacokinetics · 2008Review
- Liver enzymes elevation and immune reconstitution among treatment-naïve HIV-infected patients instituting antiretroviral therapy.The American journal of the medical sciences · 2007Article
- Management and treatment of hepatitis C virus in patients with HIV and hepatitis C virus coinfection: A practical guide for health care professionals.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2007Article
- Compartmental pharmacokinetic analysis of oral amprenavir with secondary peaks.Antimicrobial agents and chemotherapy · 2007Article
- Lopinavir/ritonavir pharmacokinetics in HIV and hepatitis C virus co-infected patients without liver function impairment: influence of liver fibrosis.Clinical pharmacokinetics · 2007Article
- Fosamprenavir : clinical pharmacokinetics and drug interactions of the amprenavir prodrug.Clinical pharmacokinetics · 2006Review
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Amprenavir (141W94) is extensively metabolized by P450 cytochromes, specifically, CYP3A4. Because hepatic insufficiency reduces P450-mediated metabolism, the concentrations in plasma of drugs metabolized through this pathway are often increased in subjects with liver disease. Following administration of a single, oral dose of 600 mg of amprenavir, pharmacokinetic parameters were determined for 10 subjects with severe cirrhosis, 10 subjects with moderate cirrhosis, and 10 healthy volunteers. Model-independent methods for determining the area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC(0-infinity)) showed an increase in amprenavir AUC(0-infinity) of 2.5-fold in the group with moderate cirrhosis and 4.5-fold in the group with severe cirrhosis compared with that in the control group of healthy volunteers (P < 0.05). AUC(0-infinity) was linearly related to the severity of liver disease, as assessed by the Child-Pugh score. Of the laboratory data used to calculate the Child-Pugh score, only the mean total bilirubin concentration showed a significant relationship with AUC(0-infinity). The relationship between the total bilirubin concentration and the AUC(0-infinity) of amprenavir was well characterized by a simple E(max) model, suggesting that the total bilirubin concentration may be a useful parameter for predicting the amprenavir AUC in subjects with hepatic insufficiency. Finally, the sera of cirrhotic subjects showed significant decreases in the levels of alpha(1)-acid glycoprotein, the primary plasma binding protein for amprenavir. On the basis of the results of this study, for an exposure equivalent to a clinical dose of 1,200 mg twice daily in subjects without cirrhosis, subjects with Child-Pugh scores of 5 to 8 should receive a twice-daily 450-mg dose of amprenavir, and subjects with Child-Pugh scores of 9 to 15 should receive a twice-daily 300-mg dose of amprenavir.
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