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Opioid Concentrations in Oral Fluid and Plasma in Cancer Patients With Pain

Tarja Heiskanen, Kaarina Langel, Teemu Gunnar, Pirjo Lillsunde, Eija Kalso

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Abstract

Abstract Context Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. Objectives To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. Methods We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone, or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. Results A total of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R2 = 0.628 and 0.700, respectively), but not morphine (R2 = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL vs. plasma concentrations of oxycodone compared with morphine and fentanyl. Conclusion OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results.

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Abstract Context Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. Objectives To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. Methods We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone, or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. Results A total of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R2 = 0.628 and 0.700, respectively), but not morphine (R2 = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL vs. plasma concentrations of oxycodone compared with morphine and fentanyl. Conclusion OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results.

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Available abstract

Abstract Context Measuring opioid concentrations in pain treatment is warranted in situations where optimal opioid analgesia is difficult to reach. Objectives To assess the usefulness of oral fluid (OFL) as an alternative to plasma in opioid concentration monitoring in cancer patients on chronic opioid therapy. Methods We collected OFL and plasma samples from 64 cancer patients on controlled-release (CR) oral morphine, CR oral oxycodone, or transdermal (TD) fentanyl for pain. Samples were obtained on up to five separate days. Results A total of 213 OFL and plasma samples were evaluable. All patients had detectable amounts of the CR or TD opioid in both plasma and OFL samples. The plasma concentrations of oxycodone and fentanyl (determination coefficient R2 = 0.628 and 0.700, respectively), but not morphine (R2 = 0.292), were moderately well correlated to the daily opioid doses. In contrast to morphine and fentanyl (mean OFL/plasma ratio 2.0 and 3.0, respectively), the OFL oxycodone concentrations were significantly higher than the respective plasma concentrations (mean OFL/plasma ratio 14.9). An active transporter could explain the much higher OFL vs. plasma concentrations of oxycodone compared with morphine and fentanyl. Conclusion OFL analysis is well suited for detecting the studied opioids. For morphine and fentanyl, an approximation of the plasma opioid concentrations is obtainable, whereas for oxycodone, the OFL/plasma concentration relationship is too variable for reliable approximation results.

Key concepts: Oxycodone, Fentanyl, Morphine, Opioid, Cancer pain, Plasma concentration, Context (archaeology), Medicine

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