Projects

This portfolio showcases ongoing projects using PKRxiv datasets to answer clinically relevant questions, develop and validate models, and generate new evidence. Click a project to see the datasets used, the primary aim, and the lead investigator.

PBPK modelling of maraviroc dosing during pregnancy and rifampin co‑administration

Requested Data: Angela Colbers, Brookie Best, Stein Schalkwijk, et al. (2025). Maraviroc Pharmacokinetics in HIV-1–Infected Pregnant Women (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/FJPQ-EM93
Primary Aim: To validate a physiologically based pharmacokinetic (PBPK) model of maraviroc in pregnancy and to predict optimal maraviroc dosing in pregnant individuals during co‑administration with rifampin.
Lead Investigator: Nguyen Dat
Affiliation: Department of Clinical Pharmacology, Mahidol‑Oxford Research Unit, Thailand

Physiologically based pharmacokinetic modeling of rilpivirine to support dose optimization in pregnant women living with HIV

Requested Data: Anna H. Tran, Brookie M. Best, Alice Stek, et al. (2025). Pharmacokinetics of Rilpivirine in HIV-Infected Pregnant Women (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/2988-2541
Primary Aim: To develop and validate a PBPK model of rilpivirine and evaluate dose optimization strategies in pregnant women living with HIV.
Lead Investigator: Jeremiah D. Momper
Affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California - San Diego, USA

Population pharmacokinetic modelling and limited sampling strategy development for raltegravir in pregnancy

Requested Data: D. Heather Watts, et al. (2025). Raltegravir Pharmacokinetics During Pregnancy (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/3W7Y-FW08
Primary Aim: To develop a population pharmacokinetic (popPK) model of raltegravir using NONMEM and to derive a limited sampling strategy to support therapeutic drug monitoring in pregnant patients.
Lead Investigator: Ana Flávia Mendes Batista
Affiliation: General Hospital of Ribeirão Preto Medical School, University of São Paulo, Brazil

Utilising clinical pharmacokinetic data to reassess a legacy pregnancy PBPK model for efavirenz

Requested Data: Tim R. Cressey, et al. (2025). Efavirenz Pharmacokinetics During the Third Trimester of Pregnancy and Postpartum (dataset). PKRxiv, University of Liverpool. PKRxivStudy-0011: https://doi.org/10.58033/QXYN-NX97; Oluwasegun Eniayewu, et al. (2025). Pharmacogenetics of Efavirenz Exposure in Cervicovaginal Fluid during Pregnancy and Postpartum (dataset). PKRxiv, University of Liverpool. PKRxivStudy-0010: https://doi.org/10.58033/G748-JP07; A Olagunju, et al. (2025). Pharmacogenetics of pregnancy‐induced changes in efavirenz pharmacokinetics (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/NMMY-PR11
Primary Aim: To evaluate the performance of an existing efavirenz pregnancy PBPK model by integrating newly curated clinical PK data, thereby illustrating its utility.
Lead Investigator: Shakir Atoyebi
Affiliation: Department of Biochemistry, Cell and Systems Biology, University of Liverpool, Liverpool, UK

Real‑world analysis of antiviral drug exposure variability and adverse outcomes in pregnancy

Requested Data: Olagunju A, et al. (2025). Pharmacogenetics of pregnancy‐induced changes in efavirenz pharmacokinetics (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/NMMY-PR11; Olagunju A, et al. (2025). Breast Milk Pharmacokinetics of Efavirenz and Breastfed Infants' Exposure in Genetically Defined Subgroups of Mother-Infant Pairs: An Observational Study (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/HSNE-WC63; Akinloye A, et al. (2025). Validation and Clinical Application of a Liquid Chromatography–Ultraviolet Detection Method to Quantify Dolutegravir in Dried Blood Spots (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/JVM0-KJ86; Olagunju A, et al. (2025). Pharmacogenetics of Nevirapine Excretion into Breast Milk and Infants’ Exposure Through Breast Milk Versus Postexposure Prophylaxis (dataset) PKRxiv, University of Liverpool. https://doi.org/10.58033/EG8J-V638; Olagunju A, et al. (2025). Pregnancy affects nevirapine pharmacokinetics (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/KBJW-QC26; Waitt C, et al. (2025). Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomised trial (DolPHIN-1 study) (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/P2TT-XC95; Mulligan N, et al. (2025). Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/V0TF-XJ82
Primary Aim: To explore variability in antiviral drug exposure and associated adverse outcomes during pregnancy using real‑world data, identify sources of variability and evidence gaps, and benchmark findings against a Portuguese hospital cohort to support safer, more effective dosing strategies.
Lead Investigator: Bárbara Costa
Affiliation: University of Porto, Portugal

Benchmarking PK model fitting and cross-validation workflows in Phoenix WinNonlin vs nlmixr2 (R)

Requested Data: Akinloye A, et al. (2025). Atazanavir/Ritonavir Increased Tizoxanide Exposure from Oral Nitazoxanide through Pharmacokinetic Interaction in Healthy Volunteers (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/W4VY-7Q28
Primary Aim: To practice PK data fitting and model cross-validation and to compare the performance of models developed using Phoenix WinNonlin (WNL) and nlmixr2 in R.
Lead Investigator: Ivy Wu
Affiliation: N/A

Machine learning prediction of efavirenz exposure using a limited sampling strategy

Requested Data: Olagunju A, et al. (2025). Pharmacogenetics of pregnancy‐induced changes in efavirenz pharmacokinetics (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/NMMY-PR11
Primary Aim: To develop and validate machine learning models in R to predict efavirenz plasma exposure from limited sampling time points, improving clinical relevance for personalized dosing.
Lead Investigator: Nathan Nakao
Affiliation: University of São Paulo, Brazil

Machine learning prediction of dolutegravir AUC with external validation and development of a limited sampling strategy

Requested Data: Waitt C, et al. (2025). Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomised trial (DolPHIN-1 study) (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/P2TT-XC95; Mulligan N et al. (2025). Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/V0TF-XJ82
Primary Aim: To develop and externally validate machine learning models (SVM, XGBoost, Lasso/Elastic-Net GLMs, Random Forest) for predicting dolutegravir AUC, and—if performance is adequate—to derive a limited sampling strategy using sparse early plasma samples to reduce patient burden while maintaining prediction accuracy/precision
Lead Investigator: Matheus De Lucca Thomaz
Affiliation: University of São Paulo, Brazil

Predicting Concentration of Nevirapine Using a Novel PK/Machine Learning Method

Requested Data: Olagunju A, et al. (2025). Pregnancy affects nevirapine pharmacokinetics (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/KBJW-QC26
Primary Aim: To develop and evaluate a novel pharmacokinetic/machine learning hybrid model to predict nevirapine concentrations in treated patients, and to compare its precision and predictive performance against a PKPD modeling approach.
Lead Investigator: Elham Haem
Affiliation: Shiraz University of Medical Sciences, Iran

Population PK modelling and limited sampling strategy optimisation for dolutegravir in pregnancy and postpartum

Requested Data: Waitt C, et al. (2025). Safety and pharmacokinetics of dolutegravir in pregnant mothers with HIV infection and their neonates: A randomised trial (DolPHIN-1 study) (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/P2TT-XC95; Mulligan N et al. (2025). Dolutegravir pharmacokinetics in pregnant and postpartum women living with HIV (dataset). PKRxiv, University of Liverpool. https://doi.org/10.58033/V0TF-XJ82
Primary Aim: To develop a population pharmacokinetic (popPK) model of dolutegravir using a limited sampling strategy (LSS) approach, in order to identify optimal sampling times and improve therapeutic drug monitoring strategies in pregnant and postpartum women.
Lead Investigator: Álef Machado Gomes Pego
Affiliation: University of São Paulo, Brazil