Trial reportClinical pharmacokinetics2005
High variability of indinavir and nelfinavir pharmacokinetics in HIV-infected patients with a sustained virological response on highly active antiretroviral therapy.
Trial report in Clinical pharmacokinetics, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Can we Predict Drug Excretion into Saliva? A Systematic Review and Analysis of Physicochemical Properties.Clinical pharmacokinetics · 2024Pooled it
- Pharmacokinetic modelling of efavirenz, atazanavir, lamivudine and tenofovir in the female genital tract of HIV-infected pre-menopausal women.Clinical pharmacokinetics · 2012Trial
- Population pharmacokinetic-pharmacogenetic study of nevirapine in HIV-infected Cambodian patients.Antimicrobial agents and chemotherapy · 2010Trial
- Predictive values of the human immunodeficiency virus phenotype and genotype and of amprenavir and lopinavir inhibitory quotients in heavily pretreated patients on a ritonavir-boosted dual-protease-inhibitor regimen.Antimicrobial agents and chemotherapy · 2008Trial
- Comparison of model-based tests and selection strategies to detect genetic polymorphisms influencing pharmacokinetic parameters.Journal of biopharmaceutical statistics · 2008Trial
- Population pharmacokinetic analysis of lamivudine, stavudine and zidovudine in controlled HIV-infected patients on HAART.European journal of clinical pharmacology · 2007Trial
- An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Clinical pharmacokinetics of antiretroviral drugs in older persons.Expert opinion on drug metabolism & toxicology · 2013Review
- Nelfinavir, an HIV-1 protease inhibitor, induces oxidative stress-mediated, caspase-independent apoptosis in Leishmania amastigotes.PLoS neglected tropical diseases · 2010Article
- Influence of pharmacogenetics on indinavir disposition and short-term response in HIV patients initiating HAART.European journal of clinical pharmacology · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesTo describe plasma concentrations of indinavir alone or combined with ritonavir, and of nelfinavir and its active metabolite M8, and to measure their variabilities in HIV-infected patients treated with a stable antiretroviral regimen and experiencing a sustained virological response for at least 12 months. PATIENTS AND
methodsIn this prospective trial, blood samples were drawn during a 6-hour time interval between two doses at enrolment to assess protease inhibitor (PI) pharmacokinetic parameters, and 4 months later to assess plasma trough and peak concentrations. Safety and adherence assessments and laboratory data were collected during an 8-month period. PI pharmacokinetic characteristics were analysed using a non-compartmental approach. Inter- and intrapatient variabilities were estimated using a linear mixed-effect model. The impact of different covariates on plasma trough concentrations was investigated. Eighty-eight patients were analysed: 42 treated with indinavir and 46 with nelfinavir.
resultsThe interquartile range (IQR) of the plasma trough concentration corrected for the sampling time (Ccalc) was 116-374 microg/L for indinavir alone and 163-508 microg/L for indinavir/ritonavir. Ritonavir significantly increased indinavir elimination half-life and plasma exposure. For nelfinavir, the IQR of Ccalc was 896-2059 microg/L for three-times-daily administration and 998-2124 microg/L for twice-daily administration. Variabilities were high for both PIs. Intrapatient variability for indinavir alone (and indinavir + ritonavir) was 76% (107%) and interpatient variability was 58% (10%) in adherent patients. Intrapatient variability for nelfinavir three times daily (and twice daily) was 41% (74%) and interpatient variability was 62% (50%). Intrapatient variability was lowered in patients with a high adherence level.
conclusionAlthough performed in a homogeneous population, this study documented a high interpatient but also intrapatient variability of indinavir and nelfinavir pharmacokinetics, which should be taken into account when interpreting therapeutic drug monitoring. Once patients have reached a sustained virological response, plasma PI monitoring may have a limited impact.
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