Trial reportClinical pharmacokinetics1999
Relationships between exposure to saquinavir monotherapy and antiviral response in HIV-positive patients.
Trial report in Clinical pharmacokinetics, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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
28 citing papers in PubMed, 99 citations in OpenAlex.
- Clinical and pharmacokinetic data support once-daily low-dose boosted saquinavir (1,200 milligrams saquinavir with 100 milligrams ritonavir) in treatment-naive or limited protease inhibitor-experienced human immunodeficiency virus-infected patients.Antimicrobial agents and chemotherapy · 2007Trial
- Efficacy, safety and pharmacokinetics of once-daily saquinavir soft-gelatin capsule/ritonavir in antiretroviral-naive, HIV-infected patients.MedGenMed : Medscape general medicine · 2006Trial
- Intracellular and plasma pharmacokinetics of saquinavir-ritonavir, administered at 1,600/100 milligrams once daily in human immunodeficiency virus-infected patients.Antimicrobial agents and chemotherapy · 2004Trial
- Pharmacokinetics of saquinavir plus low-dose ritonavir in human immunodeficiency virus-infected pregnant women.Antimicrobial agents and chemotherapy · 2004Trial
- Interaction between saquinavir soft-gel and rifabutin in patients infected with HIV.British journal of clinical pharmacology · 2002Trial
- Saquinavir and ritonavir pharmacokinetics following combined ritonavir and saquinavir (soft gelatin capsules) administration.British journal of clinical pharmacology · 2001Trial
- Pharmacological basis for concentration-controlled therapy with zidovudine, lamivudine, and indinavir.Antimicrobial agents and chemotherapy · 2001Trial
- Pharmacokinetic and pharmacodynamic study of the human immunodeficiency virus protease inhibitor amprenavir after multiple oral dosing.Antimicrobial agents and chemotherapy · 2001Trial
- Article
- Integrated population pharmacokinetic/viral dynamic modelling of lopinavir/ritonavir in HIV-1 treatment-naïve patients.Clinical pharmacokinetics · 2014Article
- Novel method to assess antiretroviral target trough concentrations using in vitro susceptibility data.Antimicrobial agents and chemotherapy · 2012Article
- An example of optimal phase II design for exposure response modelling.Journal of pharmacokinetics and pharmacodynamics · 2010Article
- Efficacy, safety and pharmacokinetic of once-daily boosted saquinavir (1500/100 mg) together with 2 nucleos(t)ide reverse transcriptase inhibitors in real life: a multicentre prospective study.AIDS research and therapy · 2010Article
- Variability in non-nucleoside reverse transcriptase and protease inhibitors concentrations among HIV-infected adults in routine clinical practice.British journal of clinical pharmacology · 2007Article
- Variability in non-nucleoside reverse transcriptase and protease inhibitor concentrations among HIV-infected adults in routine clinical practice.British journal of clinical pharmacology · 2006Article
- Application and impact of population pharmacokinetics in the assessment of antiretroviral pharmacotherapy.Clinical pharmacokinetics · 2005Review
- Therapeutic drug monitoring of lopinavir/ritonavir given alone or with a non-nucleoside reverse transcriptase inhibitor.British journal of clinical pharmacology · 2004Article
- Updated clinical pharmacologic considerations for HIV-1 protease inhibitors.Current HIV/AIDS reports · 2004Review
- High variability of plasma drug concentrations in dual protease inhibitor regimens.Antimicrobial agents and chemotherapy · 2003Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe aim of this study was to confirm the most appropriate dosage of a new soft gelatin capsule (SGC) formulation of the HIV protease inhibitor saquinavir by investigating the relationships between systemic (plasma) exposure to saquinavir and plasma HIV RNA and CD4+ cell counts using empirical mathematical modelling. DESIGN AND
settingA randomised, non-blind, multicentre, dose-ranging 8-week study of monotherapy with 400, 800 or 1200 mg of saquinavir-SGC or 600 mg of the hard gelatin capsule (HGC) formulation, both administered 3 times daily, was carried out in protease inhibitor-naive, HIV-positive adults. Two surrogate markers of response, plasma HIV RNA level and CD4+ cell count, were fitted to 2 measures of systemic drug exposure, the area under the plasma concentration-time curve (AUC) and trough plasma concentration (Cmin), using 6 exposure-response models of progressively increasing complexity. Akaike and Schwarz model selection criteria were applied to determine the most effective pharmacokinetic-pharmacodynamic relationship.
resultsA total of 88 patients were randomised; pharmacokinetic and pharmacodynamic data were available for 84 patients. In terms of plasma HIV RNA, pharmacokinetic-pharmacodynamic relationships were best described by a 2-parameter maximum effect (Emax) model, which predicted a typical maximum reduction in viral load of 1.94 log10 copies/ml [coefficient of variation (CV) 12%], with a half-maximal antiviral response occurring at a Cmin of 50 micrograms/L (CV 40%). Saquinavir-SGC 1200 mg administered 3 times daily produced a median AUC to 24 hours (AUC24) of approximately 20,000 micrograms/L.h, corresponding to 85% of the maximum achievable antiviral effect as defined by the model. None of the models yielded a satisfactory fit for CD4+ cell count.
conclusionEmpirical mathematical modelling confirmed that, when administered 3 times daily, the optimum dose of saquinavir-SGC is 1200 mg, corresponding to 3600 mg/day.
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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.