Impact of Sampling Window Variability on Pharmacokinetic Parameters Estimated by Non-Compartmental Analysis: Case Studies of Various Types of Drugs

Clin Pharmacol Drug Dev. 2026 Jan;15(1):e70004. doi: 10.1002/cpdd.70004.

Abstract

Non-compartmental analysis (NCA) is commonly used to estimate pharmacokinetic (PK) parameters in individual participants during Phase 1 studies. PK sampling schedules are important for accurately characterizing a drug's PK profile. However, collecting blood samples on time is often challenging, even in Phase 1 studies involving healthy participants, due to tightly scheduled study activities. To address these constraints, sampling windows-defined as permissible time intervals for blood sample collection-are often implemented. These windows provide operational flexibility at clinical study sites while maintaining a reasonable level of accuracy in parameter estimation. To date, no published literature has described the construction of sampling windows for NCA, and the general practice of constructing sampling windows remains unstandardized. In this study, we evaluated the impact of varying sampling window lengths on NCA-derived PK parameters, leveraging bioequivalence criteria as an indicator to assess the effects and provide insights into the construction of sampling windows for NCA. As a result, we were able to quantitatively evaluate how changes in sampling window length affect NCA-based PK parameters. Based on these findings, we provide recommendations for appropriate sampling windows.

Keywords: anakinra; lorlatinib; non‐compartmental analysis; relebactam; sampling window.

MeSH terms

  • Blood Specimen Collection* / methods
  • Clinical Trials, Phase I as Topic / methods
  • Healthy Volunteers
  • Humans
  • Male
  • Models, Biological*
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / blood
  • Pharmacokinetics*
  • Therapeutic Equivalency
  • Time Factors

Substances

  • Pharmaceutical Preparations