Hi all, Happy New Year to everyone! I’m starting a new series this year called #ScienceJournalJourney where I review an interesting journal article and give a quick layman summary on it. As your favorite post doc influencer on LinkedIn, I will be mainly focusing on journals related to pharmacology and pharmacometrics.

Let’s begin our series with a nice paper from the Clinical and Translational Science journal titled “Population pharmacokinetics of iruplinalkib in healthy volunteers and patients with solid tumors”, by GH Yang et al. https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.70099

According to the American Cancer Society, non small cell lung cancer (NSCLC) also has a dismal overall survival rate of 28%, hence new therapies such as iruplinalkib are sorely needed.

However,  the same dose of drug can give different drug levels, depending on a patient’s demographics, such as their weight, renal and liver function. The differing drug levels can impact whether a patient experiences severe toxicity or a lack of efficacy. During early clinical trials, these drug levels are collected from patients. Population pharmacokinetics models such as the one described in the paper are then used to find the reasons for variability in drug levels. This was done by first building a base model that describes all data, and then employing step-wise covariate modeling, where the patient demographics of weight, renal and liver function are tested to explain the model variability. The demographics that describe the variability best are selected to be part of the model as a factor that impacts model parameters such as drug clearance, which can impact drug levels. Knowing which covariates impact the drug’s levels can thus help the manufacturers recommend when a drug’s dose might be adjusted.

In this study, as all the covariates did not result in a change in drug exposure beyond the tolerated range of 0.8-1.25 fold from the population average, the investigators recommended no dose adjustment was necessary. This study however, had limited patients with severe liver or renal impairment, making it inconclusive if such patients would require special dose adjustments, which the investigators acknowledged.

This is a standard study often reported in clinical pharmacology journals for developing new drugs. It is, however, important to report this information to help other researchers and clinicians make decisions for subsequent trials. This was a nice, easy read with all the relevant evidence including model building diagnostics reported and a great paper to start our series!