Importance Of Pharmacokinetic (PK) Drug Studies In Drug Discovery And Development

The basic concepts of what has emerged as pharmacokinetic studies, better known as PK studies, developed in the 1960s. However, specific developments in the bioanalytical, conceptual, experimental, and mathematical fields were necessary before PK assays could become an integral part of the drug discovery and development process. 

That took a couple of decades. PK studies, thus, emerged as an indispensable part of pharmaceutical bioanalytics since the mid-1980s. There have been significant signs of progress since then as well. Together with drug metabolism, PK assays have evolved into what we now know as DMPK science.  

The Basics of a Pharmacokinetic Study

In the simplest terms, a Pharmacokinetic Study focuses on understanding what the organism does to a drug post administering it. PK assays for drug discovery and development typically look at four processes: absorption, distribution, metabolism, and elimination/excretion (ADME). 

The quantitative measurement of a drug’s PK through the ADME processes using different biological matrices reflects the duration and intensity of the drug. Blood, plasma, saliva, and urine are the typical matrices used.

Pharmacokinetics studies remain important throughout the drug discovery and development process. However, their focus changes as the process progresses. At the discovery stage, PK studies aim at selecting the target or the molecule. During the preclinical and clinical trial phases, PK assays focus on dosage and safety aspects. 

PK Assays & GLP Standards

One of the most prevalent compliance needs for PK assays relates to good laboratory practice (GLP) standards. The World Health Organization (WHO) in collaboration with TDR published the second edition of a handbook on GLP standards in 2009. TDR is WHO’s special program for research and training in tropical diseases. 

This handbook informs that the GLP concept originated in the USA way back in the 1970s. GLP regulations have since been included in the national legislations of several OECD countries including the European Union and the USA. 

Since the turn of the millennium, GLP standards are internationally mandatory for valid data exchange on PK assays and other studies involved in drug development. These are regulatory standards that relate to the entire process of the nonclinical stage of drug development. 

The aim of GLP regulations is to ensure that drug development happens according to a set of standards that ensure “the quality, reliability and integrity of studies, the reporting of verifiable conclusions and the traceability of data” (WHO & TDR, 2009, p.7). 

It is not a regulatory need to apply GLP standards to the early stage of drug discovery that focuses on the feasibility of a new chemical entity as a drug candidate. However, following GLP standards even at the discovery stage makes early PK studies more cost-effective, experts say. 

Recent Developments in PK Studies

The WorldWide Antimalarial Resistance Network (WWARN) issued new procedural guidelines to blood PK sample processing and transport in 2018. Several PK studies targeting anti-drug antibodies for the production of biosimilar products have been reported in recent articles. 

This has emerged as an important field of study as several patents for approved biologics will expire in 2020. 

The FDA in July 2019 issued draft guidelines for population PK studies. Population PK studies get routinely conducted to identify needs for individualization of therapeutics, such as specifying dosages for varying patient populations and/or disease situations. 

The FDA recommends adequate population PK data collection prior to marketing applications for new drugs. That can mitigate post-marketing commitments and requirements.