Sources of preanalytical error in pharmacokinetic analyses – focus on intravenous drug administration and collection of blood samples

Abstract

Introduction: Pharmacokinetic (PK) studies for long-established drugs are generally performed outside the well-standardized settings of pharmaceutical industry trials. Instead, such studies are usually performed within daily clinical practice of hospitals.

Areas covered: This article describes aspects of intravenous (i.v.) drug administration and blood sampling that contribute to potential sources of preanalytical errors for PK investigations. Parameters that bias determination of start and end time of i.v. infusions, as well as consistent rate of drug delivery, are discussed. Causes for drug loss in the infusion device, including adsorption and insufficient flushing, are outlined. The advantages and disadvantages of different blood sampling techniques are reviewed, with an emphasis on pediatric studies.

Expert opinion: For PK studies that are integrated into the general hospital routine, a variety of potential sources of error exist. Potential pitfalls depend on the specific drug and trial characteristics and they must be anticipated and discussed in advance. Working procedures need to be developed that address the anticipated problems and in detail describe procedures that need compliance between bed and bench.

Keywords::

• blood sampling
• drug adsorption
• drug delivery
• intravenous infusion
• pharmacokinetic studies

Acknowledgment

The authors want to thank Dr Nina Kontny, Dr Gudrun Würthwein and Svantje Völler for helpful discussions during preparation of the manuscript.

Declaration of interest

The authors were supported by the European Community's Seventh Framework Programme under grant agreement number 222910. Dr Krischke is working at the German Federal Ministry of Education and Research (BMBF)-funded Centre for Clinical Trials Münster (01KN1105). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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