ArticleClinical pharmacokinetics2014
Integrated population pharmacokinetic/viral dynamic modelling of lopinavir/ritonavir in HIV-1 treatment-naïve patients.
Article in Clinical pharmacokinetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- No Need for Lopinavir Dose Adjustment during Pregnancy: a Population Pharmacokinetic and Exposure-Response Analysis in Pregnant and Nonpregnant HIV-Infected Subjects.Antimicrobial agents and chemotherapy · 2016Trial
- Investigational Treatments for COVID-19 may Increase Ventricular Arrhythmia Risk Through Drug Interactions.CPT: pharmacometrics & systems pharmacology · 2021Article
- Timing of Antiviral Treatment Initiation is Critical to Reduce SARS-CoV-2 Viral Load.CPT: pharmacometrics & systems pharmacology · 2020Article
- Investigational treatments for COVID-19 may increase ventricular arrhythmia risk through drug interactions.medRxiv : the preprint server for health sciences · 2020Article
- Application of physiologically based pharmacokinetic modeling to the prediction of drug-drug and drug-disease interactions for rivaroxaban.European journal of clinical pharmacology · 2018Article
- Model-Based Analysis of Unbound Lopinavir Pharmacokinetics in HIV-Infected Pregnant Women Supports Standard Dosing in the Third Trimester.CPT: pharmacometrics & systems pharmacology · 2016Article
- A Case of Long-Term Seronegative Human Immunodeficiency Virus (HIV) Infection: The Importance of the Humoral Response to HIV.Open forum infectious diseases · 2016Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundLopinavir (LPV)/ritonavir (RTV) co-formulation (LPV/RTV) is a widely used protease inhibitor (PI)-based regimen to treat HIV-infection. As with all PIs, the trough concentration (C trough) is a primary determinant of response, but the optimum exposure remains poorly defined. The primary objective was to develop an integrated LPV population pharmacokinetic model to investigate the influence of α-1-acid glycoprotein and link total and free LPV exposure to pharmacodynamic changes in HIV-1 RNA and assess viral dynamic and drug efficacy parameters.
methodsData from 35 treatment-naïve HIV-infected patients initiating therapy with LPV/RTV 400/100 mg orally twice daily across two studies were used for model development and simulations using ADAPT. Total LPV (LPVt) and RTV concentrations were measured by high-performance liquid chromatography with ultraviolet (UV) detection. Free LPV (LPVf) concentrations were measured using equilibrium dialysis and mass spectrometry.
resultsThe LPVt typical value of clearance (CLLPVt/F) was 4.73 L/h and the distribution volume (VLPVt/F) was 55.7 L. The clearance (CLLPVf/F) and distribution volume (Vf/F) for LPVf were 596 L/h and 6,370 L, respectively. The virion clearance rate was 0.0350 h(-1). The simulated LPVLPVt C trough values at 90% (EC90) and 95% (EC95) of the maximum response were 316 and 726 ng/mL, respectively.
conclusionsThe pharmacokinetic-pharmacodynamic model provides a useful tool to quantitatively describe the relationship between LPV/RTV exposure and viral response. This comprehensive modelling and simulation approach could be used as a surrogate assessment of antiretroviral (ARV) activity where adequate early-phase dose-ranging studies are lacking in order to define target trough concentrations and possibly refine dosing recommendations.
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