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Clinically relevant concentrations of opioids for in vitro studies

Jason W. Boland, FRCP, PhD, A. Graham Pockley, PhD


Objectives: Numerous in vitro studies have evaluated the influence of opioids on many biological and immunological processes. The concentrations that have been used in these studies span a large range and often do not reflect levels that are present in the relevant patient groups. This article reviews the literature concerning the concentrations of opioids that are detected in patients so that the concentrations of opioids that are used for in vitro studies can better reflect those that are present clinically. This will enable scientists and clinicians to more effectively model and interpret potentially relevant clinical effects from in vitro studies.

Methods: Data on the concentrations of six commonly used opioids from clinical studies in adults were collected by searching PubMed (Medline).

Results: A total of 42 relevant studies were included in the review. Concentrations of the opioids from previous clinical studies were mostly between 1 and 10 ng/mL for buprenorphine, 1 and 10 ng/mL for fentanyl, 50 and 500 ng/mL for methadone, 25 and 250 ng/mL for morphine, 10 and 100 ng/mL for oxycodone, and 100 and 1,000 ng/mL for Tramadol and were dependent on the patient group and indication under investigation.

Conclusions: Concentrations of opioids used in vitro should include those that are present in the relevant clinical setting if the effects of opioids detected in vitro are to be of potential relevance to the clinical setting. Therefore, it is essential that these concentrations in the relevant clinical context(s) are known.


opioid, concentration, in vitro, clinical studies, human studies, cancer pain

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