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In some cases, data on the ability of these alternatives to depress respiration alone or in conjunction with an opioid are lacking. A nonclinical in vivo model was developed that could detect worsening respiratory depression when a benzodiazepine (diazepam) was used in combination with an opioid (oxycodone) compared to the opioid alone based on an increased arterial partial pressure of carbon dioxide (pCO<jats:sub>2<\/jats:sub>). The current study used that model to assess the impact on respiration of non\u2010benzodiazepine sedative psychotropic drugs representative of different drug classes (clozapine, quetiapine, risperidone, zolpidem, trazodone, carisoprodol, cyclobenzaprine, mirtazapine, topiramate, paroxetine, duloxetine, ramelteon, and suvorexant) administered alone and with oxycodone. At clinically relevant exposures, paroxetine, trazodone, and quetiapine given with oxycodone significantly increased pCO<jats:sub>2<\/jats:sub> above the oxycodone effect. Analyses indicated that most pCO<jats:sub>2<\/jats:sub> interaction effects were due to pharmacokinetic interactions resulting in increased oxycodone exposure. Increased pCO<jats:sub>2<\/jats:sub> recorded with oxycodone\u2010paroxetine co\u2010administration exceeded expected effects from only drug exposure suggesting another mechanism for the increased pharmacodynamic response. This study identified drug\u2010drug interaction effects depressing respiration in an animal model when quetiapine or paroxetine were co\u2010administered with oxycodone. Clinical pharmacodynamic drug interaction studies are being conducted with these drugs to assess translatability of these findings.<\/jats:p>","DOI":"10.1111\/cts.13080","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T09:02:30Z","timestamp":1622797350000},"page":"2208-2219","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat"],"prefix":"10.1111","volume":"14","author":[{"given":"Lin","family":"Xu","sequence":"first","affiliation":[{"name":"Division of Applied Regulatory Science Office of Clinical Pharmacology Office of Translational Sciences Center for Drug Evaluation and Research US Food and Drug Administration Silver Spring Maryland 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