Modern drug development relies on efficient and accurate data analysis and interpretation. Currently, a number of distinct approaches to the analysis of pharmacokinetic data are available to drug developers. Thus, it is important that the development team selects the optimal approach for a particular task or application. Panels A to C in the plot above represent three different approaches to pharmacokinetic data analysis. For each of these approaches, describe in your own words two applications for which you would use them, and why the approach is particularly suited to these applications. 

Discuss what the profiles tell you about how this drug candidate might act. 

Which PK/PD model/s would you recommend to describe these profiles? Explain which characteristics of the curves enable you to draw your conclusion. 

Many drugs are still administered as a ‘one size fits all’, i.e. the same dose and dosage regimen is given to all patients. However currently there is a push towards individualised dosing, also called ‘precision medicine’. Which approaches might you consider to individualise dosing with this new antibiotic? 

A new antibiotic against difficult to treat bacteria has been studied in patients with a wide range of renal functions. The graphs show the probability of attaining the PK/PD target (PTA) of 50% fT>MIC for two different dosage regimens. The PTA profiles are presented for three different groups stratified by creatinine clearance (CLCR, mL/min). Interpret the graphs and discuss what they tell you about dosing of future target patient populations with this new antibiotic. 

Describe whether there is any further information that you would like to know about this drug candidate, in order to help you decide which subject characteristic is the most useful covariate. If yes, which information would you request from the drug development team and why? 

Discuss, for each of the panels, how useful the subject characteristic that is plotted is likely to be in order to explain the interindividual variability in clearance between the subjects in the study, and to ultimately inform dosing. Include the rationale for your conclusions.

What approaches to data analysis would you recommend being performed in order to support the decision whether this regimen should be approved for clinical use in patients, and why?

Discuss whether this dosage regimen should be recommended for use in future target patient populations. Is there any additional information that you might want to request from the study team in order to draw your conclusion, and if yes, which information? 

What are excipients, and what roles do they play in ibuprofen tablet formulation?

Hint: Think about how excipients such as binders, disintegrants, lubricants, and fillers affect the tablet’s integrity, disintegration, dissolution, and stability.