Clinical Pharmacology

Perhaps the key question underlying the drug development process is, what is the optimal dose? For every candidate drug there is a dose and regimen at which the benefit-risk is optimally balanced. In early clinical development, it is the task of the drug developer to discover in the most efficient manner (in terms of time and cost) whether the drug has the potential to be of value in brining benefits to patients – is it worth investing in, does it have the potential to become a valuable drug? In later clinical development, the task is simply to demonstrate convincingly patient-benefit – using the best dose and regimen discovered earlier in the development process. 

Clinical pharmacology supports both the early clinical development stage by providing the technology and thinking to make decisions on drug value as well as providing dose adjustment directions according to the specifics of the patient and the conditions in which the patient takes the drug.

Interestingly the FDA clinical pharmacology reviewers are guided by four simple but enlightening questions: 

1. To what extent does the available clinical pharmacology information provide pivotal or supportive evidence of effectiveness?
2. Is the proposed dosing regimen appropriate for the general patient population for which the indication is being sought?
3. Is an alternative dosing regimen and/or management strategy required for subpopulations based on intrinsic factors?
4. Are there clinically relevant food-drug or drug-drug interactions, and what is      the appropriate management strategy?

The typical studies necessary to deliver on the goals described above are described below:

•  First time in man: to assess tolerability, safety, describe PK and assess pharmacological response all under single dose and multiple dose conditions
• Study impact of extrinsic factors on drug exposure and impact on dose adjustment
  • Effect of food on oral absorption
  • Effect of perpetrators of drug-drug interactions via shared metabolic clearance pathways or via shared transporter systems
• Study of impact of intrinsic factors on drug exposure and impact on dose adjustment
  • Effect of old age
  • Paediatrics
  • Renal impairment
  • Hepatic impairment
• Potential prolongation effects of candidate drug on QT/QTc interval and pro-arrhythmia
• Understanding of drug disposition
  • Absolute bioavailability
  • Absorption, distribution, metabolism and excretion of drug and metabolites
  • Biopharmaceutics
  • Bioequivalence
• Formulation development

GS Drug Development Services have over 30 years’ experience in designing, interpreting and integrating these concepts in drug development programmes.