Physiologically Based Pharmacokinetic (PBPK) modelling is a mathematical modelling technique for predicting the absorption, distribution, metabolism and excretion (ADME) of synthetic or natural chemical substances in humans and other animal species. PBPK modelling is used in pharmaceutical research and drug development, and in health risk assessment for cosmetics or general chemicals.
The January 2024 #PBPK2024 was held in Kampala, Uganda. The workshop, the first of its kind in Eastern and Southern Africa was in partnership between the Maternal and Infant Lactation pharmacoKinetics (MILK) programme at the Infectious Diseases Institute, Makerere University (IDI) and the University of Liverpool led by Professor Catriona Waitt and Professor Saskia de Wildt from Radboud University Medical Centre (RUMC). They are both current beneficiaries of funding from the Bill & Melinda Gates Foundation with specific objectives to increase the application of (PBPK) modelling to global health challenges.
#PBPK2024 was hosted by IDI in partnership with RUMC and other global partners to provide hands-on demonstration of the application of PBPK modelling. The goal was to bridge the gap between PBPK modelling specialists and decision-makers in global drug development and clinical care, in order to increase awareness of the technique with specific reference to the global health challenges affecting our populations.
Pregnant and breastfeeding women and children often face challenges in pharmacotherapy due to limited dosing information. PBPK models, validated with clinical data, offer a promising solution. While PBPK modelling is increasingly used in drug development, its application in addressing dosing questions for pregnant and lactating women is a relatively new area of application and this was the focus of the workshop.
The workshop brought together 65 delegates and 11 tutors from countries including: Uganda, Kenya, Tanzania, Zimbabwe, Nigeria, DR Congo, South Africa, Netherlands, Switzerland, France, UK, and USA. Tutors from Radboud University Medical School (Rick Greupink, Joyce van der Heijden, Charlotte Koldewiej) and SimCyp (Karen Rowland Yeo, Lisa Almond, Amita Pansari and Kelly Turton) were joined by Shakir Atoyebi, PhD student in Pharmacology and Therapeutics at the University of Liverpool. Delegates included senior Clinical Pharmacologists, clinical pharmacists, physicians and investigators from across Africa, as well as members from the Ugandan National Drug Authority.
The regulatory perspective on PBPK was covered by representatives from the UK Medicines and Healthcare Products Regulatory Agency (Essam Kerwash and Andrew Butler). Specific to the question of antimalarial use in pregnancy and breastfeeding, collaborators from the Medicines for Malaria Venture, Myriam El Gaaloul and Sonia Khier brought their expertise. Ping Zhao, Senior Project Officer from the Bill & Melinda Gate Foundation provided hands-on tuition and was supported by Jacqueline Bryan, Business Manager.
Delegates delved into the fundamentals of PBPK modelling, exploring its impact on drug development and considering crucial factors when applying these models to evaluate drug dosing in specific understudied populations. Through interactive simulations, delegates gained practical experience using PBPK models to assess the impact of physiological changes on drug disposition.
Discussions revolved around establishing the necessary framework for incorporating simulation-based evidence to inform optimal drug use. The workshop addressed regulatory aspects of PBPK modelling, providing insights into its integration into the drug development and approval process. A guided tour through clinical, research and laboratory facilities at the Infectious Diseases Institute, Makerere University enabled delegates to place their learning in context, and to interact with different study teams which we hope will foster growth of the collaborative network.
The workshop marked the first dedicated PBPK event in East Africa, laying a strong foundation for future collaborations and growth in the region. Delegates recognized the critical need to use PBPK models for addressing complex questions related to dose selection in traditionally underserved populations. All left with hands-on experience of using the software, with an appreciation of how to apply this knowledge in real-life scenarios.
The delegates were also treated to a Ugandan cultural extravaganza by way of a social evening filled with traditional folk dance, music, comedy and food, which enabled further networking and an opportunity for those new to Uganda to understand more about the context and culture.
In conclusion, the PBPK2024 workshop in Kampala was a catalyst for change, offering a promising avenue to optimize drug therapy for the most complex and understudied populations. The workshop which is believed to be the first of its kind in Africa sent a strong foundation for collaboration, networking and building a strong and committed team of PK modellers in the global south.