Addressing the FDA’s Need to Simulate Your Pharmacokinetics (PK) Exposure During Drug Development

Pharmacokinetics (PK) is the analysis of what the body does to a drug. But, Pharmacodynamics (PD) is what the drug does to the body. It is important to understand pharmacokinetics vs. pharmacodynamics. Clinical pharmacokinetic studies optimize therapy in individual patients, making it an integral part of drug development. The level of drugs in a patient’s blood decides whether a patient will have toxicity or respond to therapy. Understanding the absorption, metabolization, and elimination of a drug in the body ensures maximized potential. It leverages optimization of drug development and uses in the clinic.

The intensive nature of pharmacokinetic studies details the characterization of PK exposure parameters. Some of these include: 

  • the half-life of the drug, 
  • maximum concentration, 
  • area under the curve, and
  • trough concentration. 

This also allows assessing the change in exposure to the dosage. 

Blood levels achieved after drug administration in the body are exposure. A dose is a single component of exposure. A primary focus of drug development studies is on the right dosage. But, oncology requires understanding the optimal exposure for the patient’s benefit. It is because the margin of efficacy and safety in oncological therapeutics is small. One-dose fits all does not apply in oncological therapeutics. Exposure varies with concomitant medications, tumor burden, genetic, organ impairment, and other factors. 

Exposure-response analysis often assesses safety or efficacy. It helps in finding dosage striking balance between efficacy and its adverse events. Increased exposure with similar efficacy and increased toxicity suggest low exposure may offer similar efficacy at lowered risks. 

Dose-modification is for minimizing drug interactions or for patients with organ impairment. Exposure-response analysis helps in identifying the same.

FDA-approved prescribing information focuses on offering details of pre-existing scenarios needing dose adjustment. Addressing the FDA’s need to simulate your Pharmacokinetics exposure has its perks. This covers pre-existing cases and scenarios. It ensures a better understanding of exposure-response relationships during drug development. 

The FDA strives to make the drug label useful for clinicians by including the known, irrespective of lack of data (if it is a case). Example: The effect of organ impairment may be unknown on exposure. A summary of patients with moderate hepatic impairment treated in the efficacy trial with no unusual efficacy findings or safety is helpful. 

Including details of comedications or patients excluded from clinical trials indicate a lack of data. In such cases, proceedings should be made with caution. FDA provides as much information as available for making an educated decision for drug exposure and dose. 

As all drug development studies are FDA reviewed, PK services during drug development is also documented. It helps understand exposure-response analysis of compounds similar to the drug in question. 

Various intrinsic and extrinsic factors affect exposure. Intrinsic factors are 

  • age 
  • disease 
  • weight 
  • genetic polymorphism, etc.

Extrinsic factors are 

  • herbal products 
  • concomitant medications 
  • smoking 
  • diet 

In clinical trials, dose adjustments in patients are done with relevant considerations. FDA’s need to stimulate PH exposure during drug development studies will aid this adjustment and expert researchers can handle the requirement and protocols accurately. 

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