Is there a role for microsampling in antibiotic pharmacokinetic studies?

ABSTRACT

Introduction: Clinical pharmacokinetic studies of antibiotics can establish evidence-based dosing regimens that improve the likelihood of eradicating the pathogen at the site of infection, reduce the potential for selection of resistant pathogens, and minimize harm to the patient. Innovations in small volume sampling (< 50 μL) or ‘microsampling’ may result in less-invasive sample collection, self-sampling and dried storage. Microsampling may open up opportunities in patient groups where sampling is challenging.

Areas Covered: The challenges for implementation of microsampling to assure suitability of the results, include: acceptable study design, regulatory agency acceptance, and meeting bioanalytical validation requirements. This manuscript covers various microsampling methods, including dried blood/plasma spots, volumetric absorptive microsampling, capillary microsampling, plasma preparation technologies and solid-phase microextraction.

Expert Opinion: The available analytical technology is being underutilized due to a lack of bridging studies and validated bioanalytical methods. These deficiencies represent major impediments to the application of microsampling to antibiotic pharmacokinetic studies. A conceptual framework for the assessment of the suitability of microsampling in clinical pharmacokinetic studies of antibiotics is provided. This model establishes a ‘contingency approach’ with consideration of the antibiotic and the type and location of the patient, as well as the more prescriptive bioanalytical validation protocols.

KEYWORDS:

• Microsampling
• pharmacokinetic
• antibiotic

Article highlights

• Microsampling has the potential to open opportunities for improved clinical care where traditional blood sampling has posed challenges to the conduct of pharmacokinetic studies, including: pre-clinical studies, paediatrics, patients in remote and rural areas, and therapeutic drug monitoring.

• A variety of microsampling techniques are being investigated for use in antibiotic pharmacokinetic studies, including dried blood/plasma spots, volumetric absorptive microsampling, plasma preparation technologies, and capillary microsampling.

• The implementation of microsampling techniques for sampling in a clinical pharmacokinetic study is evaluated using a bridging study and a quantitative bioanalytical validation.

• We have developed a ‘contingency approach’ model which could be used to design a bridging study to support a quantitative bioanalytical validation – an approach where decisions for implementing microsampling are contingent on the properties of the antibiotic, as well as the type and location of the patients.

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Acknowledgments

The authors wish to thank Mr Roger Wills for his guidance in the preparation of this manuscript.

Declaration of interests

JA Roberts is a recipient of an Australian National Health and Medical Research Council Fellowship (APP1048652). We wish to acknowledge funding from the Australian National Health and Medical Research Council for Project Grants (APP1044941, APP1062040) and Centre of Research Excellence (APP1099452). 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.