• Folabomi A Oladosu, Frank F Tu, Ellen F Garrison, Katlyn E Dillane, Genevieve E Roth, and Kevin M Hellman.
• Department of Obstetrics and Gynecology, NorthShore University HealthSystem & Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA.
• Pain Med. 2020 Nov 1; 21 (11): 3102-3108.

ObjectiveIncomplete pain relief after administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is common, but it is unknown whether malabsorption or heightened metabolism contributes to NSAID resistance. To explain the etiology of NSAID resistance, we evaluated naproxen absorption and metabolism in relation to pain relief in a pilot study of women with dysmenorrhea.MethodsDuring menses, participants completed before and after naproxen ingestion pain assessments. Analgesic effectiveness was calculated as a percent change in pain rating before and after naproxen administration. To evaluate the impact of malabsorption, the correlation between analgesic effectiveness and serum naproxen was analyzed. To identify whether hypermetabolism contributes to NSAID resistance, we also analyzed the metabolite O-desmethylnaproxen.ResultsSerum naproxen and O-desmethylnaproxen concentrations of the dysmenorrheic cohort (N = 23, 126 ± 10 µg/mL, 381 ± 56 ng/mL) and healthy controls (N = 12, 135 ± 8 µg/mL, 355 ± 58 ng/mL) were not significantly different (P > 0.05), suggesting that menstrual pain does not affect drug absorption and metabolism. However, nine dysmenorrhea participants had levels of analgesic effectiveness <30%. Among dysmenorrheic women, analgesic effectiveness was correlated with serum naproxen (r = 0.49, P = 0.019) and O-desmethylnaproxen (r = 0.45, P = 0.032) concentrations. After controlling for other gynecological diagnoses, a multivariate model analysis confirmed that lower serum naproxen concentrations were associated with reduced pain relief (P  = 0.038).ConclusionsOur preliminary findings suggest that poor drug absorption contributes to ineffective pain relief in dysmenorrheic women. Future studies should explore whether malabsorption contributes to NSAID resistance for other pain conditions.© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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