PBPK for the Pill: An Approach to Assess the Risk-Benefit of Drugs
Contraception failure blamed for abortions’ was the headline of a recent article published in The Times. This was based on the results of a study performed by the British Pregnancy Advisory Service (BPAS). The study determined that more than 50% of over 60,000 females who had abortions in one of their clinics had been using some form of contraception. Thus, high contraception failure rates pose a significant burden on women.
Failure to demonstrate safety and/or efficacy contribute to the high attrition rate in drug development. A recent study of clinical trials conducted between 2001 and 2015 estimated that only 13.8% of investigational drugs eventually make it to the clinic. For this reason, one would not expect such a high percentage of therapeutic failures for approved drugs if taken correctly.
Recent years have shown a surge of population-based pharmacokinetics (PBPK) modeling and simulation within the pharmaceutical industry, and there has been strong support by global regulatory agencies for drug approvals. The positive impact that PBPK has brought to drug development has been clearly proven saving considerable time and money while also providing the ability to ask and answer many “what if” questions. For example, PBPK can account for the different intrinsic and extrinsic patient factors that can affect the pharmacokinetics (PK) of a given drug. When used during drug development, it can provide estimates of drug PK in a given population when administered alone or in combination with other drugs.
This webinar discussed how Certara’s PBPK platform, the Simcyp Simulator, was used to assess the risk-benefit profile for ethinylestradiol, the estrogen component of most combined oral contraceptives. This approach was used to identify scenarios that may bring about a loss in efficacy for some individuals. By predicting these scenarios, PBPK can help optimize the risk-benefit profile of medications.
About Our Speaker
Udoamaka (Amaka) Ezuruike is a Research Scientist in the Translational Science in DMPK team at Certara UK (Simcyp Division). She obtained a Pharmacy degree from the University of Benin in Nigeria, an MSc in Pharmacology from the University of Oxford and a PhD in Pharmaceutical Sciences from the School of Pharmacy, University College London for her research investigating pharmacokinetic herb-drug interactions amongst diabetic patients. Since joining Simcyp in 2015, she has been involved in the development and verification of both small molecule compound files and population files for the Simcyp Simulator, including the prediction of clinical drug-drug interactions involving small molecules. She is also involved in the management of the Simcyp database system.
(1) Smyth, C. Contraception failure blamed for abortions. <https://www.thetimes.co.uk/article/contraception-failure-blamed-for-abortions-w8ddnm5qz> (2017). Accessed 7 July 2017.
(2) Wong, C.H. & Kien, W.S. Estimation of clinical trial success rates and related parameters. Biostatistics 00, 1-14 (2018).