ArticlePharmacotherapy2023
Leveraging physiologically based pharmacokinetic modeling to optimize dosing for lopinavir/ritonavir with rifampin in pediatric patients.
Article in Pharmacotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 9 citations in OpenAlex.
- Physiologically Based Pharmacokinetic Modeling to Predict Lamotrigine Exposure in Special Populations to Facilitate Therapeutic Drug Monitoring and Guide Dosing Regimens.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Development of a physiologically-based pharmacokinetic model for Ritonavir characterizing exposure and drug interaction potential at both acute and steady-state conditions.CPT: pharmacometrics & systems pharmacology · 2025Article
- Application of Physiologically Based Pharmacokinetic Modeling in the Research of Anti-HIV Drugs.Current drug metabolism · 2025Review
- Physiologically-based pharmacokinetic modeling predicts the drug interaction potential of GLS4 in co-administered with ritonavir.CPT: pharmacometrics & systems pharmacology · 2024Article
- Personalized Dosing of Medicines for Children: A Primer on Pediatric Pharmacometrics for Clinicians.Paediatric drugs · 2024Review
- Predicting the correct dose in children: Role of computational Pediatric Physiological-based pharmacokinetics modeling tools.CPT: pharmacometrics & systems pharmacology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
STUDY
objectiveTreatment of HIV and tuberculosis co-infection leads to significant mortality in pediatric patients, and treatment can be challenging due to the clinically significant drug-drug interaction (DDI) between lopinavir/ritonavir (LPV/RTV) and rifampin. Doubling LPV/RTV results in insufficient lopinavir trough concentrations in pediatric patients. The objective of this study was to leverage physiologically based pharmacokinetic (PBPK) modeling to optimize the adjusted doses of LPV/RTV in children receiving the WHO-revised doses of rifampin (15 mg/kg daily).
designAdult and pediatric PBPK models for LPV/RTV with rifampin were developed, including CYP3A and P-glycoprotein inhibition and induction. SETTING (OR DATA SOURCE): Data for LPV/RTV model development and evaluation were available from the pediatric AIDS Clinical Trials Group. PATIENTS: Dosing simulations were next performed to optimize dosing in children (2 months to 8 years of age).
interventionExposure following super-boosted LPV/RTV with 10 and 15 mg/kg PO daily rifampin was simulated. MEASUREMENTS AND MAIN
resultsSimulated parameters were within twofold observations for LPV, RTV, and rifampin in adults and children ≥2 weeks old. The model predicted that, in healthy adults receiving 400/100 mg oral LPV/RTV twice daily (BID), co-treatment with 600 mg oral rifampin daily decreased the steady-state area under the concentration vs. time curve of LPV by 79%, in line with the observed change of 75%. Simulated and observed concentration profiles were comparable for LPV/RTV (230/57.5 mg/m
conclusionsSuper-boosted LPV/RTV with 15 mg/kg rifampin achieves therapeutic LPV troughs in HIV/TB-infected simulated children.
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Registered trials
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