A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats

Pilli, Nageswara Rao; Narayanasamy, Suresh; Xu, Lin; Chockalingam, Ashok; Shea, Katherine; Stewart, Sharron; Rouse, Rodney; Patel, Vikram; Matta, Murali K.

doi:10.1039/c9ra05785d

Cited by 5 publications

(5 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A few of these methods have previously been published. 29 , 30 The remaining method details are summarized in Supplementary File 0001 pages 27–32 .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat

Krishna

Stewart

et al. 2021

Clinical Translational Sci

Self Cite

View full text Add to dashboard Cite

Following a decision to require label warnings for concurrent use of opioids and benzodiazepines and increased risk of respiratory depression and death, the US Food and Drug Administratioin (FDA) recognized that other sedative psychotropic drugs may be substituted for benzodiazepines and be used concurrently with opioids. 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 (pCO2). The current study used that model to assess the impact on respiration of non‐benzodiazepine 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 pCO2 above the oxycodone effect. Analyses indicated that most pCO2 interaction effects were due to pharmacokinetic interactions resulting in increased oxycodone exposure. Increased pCO2 recorded with oxycodone‐paroxetine co‐administration exceeded expected effects from only drug exposure suggesting another mechanism for the increased pharmacodynamic response. This study identified drug‐drug interaction effects depressing respiration in an animal model when quetiapine or paroxetine were co‐administered with oxycodone. Clinical pharmacodynamic drug interaction studies are being conducted with these drugs to assess translatability of these findings.

show abstract

“…A few of these methods have previously been published. 29 , 30 The remaining method details are summarized in Supplementary File 0001 pages 27–32 .…”

Section: Methodsmentioning

confidence: 99%

“…The plasma concentrations of all drugs were measured by validated liquid chromatographic tandem mass spectrometric methods. A few of these methods have previously been published 29,30 . The remaining method details are summarized in Supplementary File 0001 pages 27–32.…”

Section: Methodsmentioning

confidence: 99%

Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat

Krishna

Stewart

et al. 2021

Clinical Translational Sci

Self Cite

View full text Add to dashboard Cite

show abstract

“…We followed bioanalytical method validation guidelines proposed by the U.S. Food and Drug Administration (FDA) 13 and published reports 14,15 to validate the present method. The validation parameters include system suitability, selectivity, specificity, sensitivity, carryover test, dilution integrity, linearity, precision and accuracy, recovery, and stability.…”

Section: Validation Experimentsmentioning

confidence: 99%

“…As an aim to develop a modest and one-step sample extraction procedure, PP was adopted for the present purpose. Moreover, PP is much affordable and easy to perform compared to solid-phase extraction (SPE) or LLE and can easily adapt the method to other laboratories [14][15][16] . Thus, PP was carried out using acetonitrile and methanol with and without the addition of extraction additives, namely ammonium acetate, formic acid, ammonium formate, etc.…”

Section: Fig 2: Positive Mode Product Ion Mass Spectra Of (A) Naftopmentioning

confidence: 99%

“…Precipitation with acetonitrile and ammonium acetate as extraction additive gave the highest recovery for the analyte without matrix effect. Stable labeled isotopes as an IS is recommended to overcome the matrix effect in LC-MS analysis [14][15][16] . Also, these standards will increase the bioanalytical assay precision and accuracy.…”

Section: Fig 2: Positive Mode Product Ion Mass Spectra Of (A) Naftopmentioning

confidence: 99%

See 1 more Smart Citation

Untitled

2021

IJPSR

View full text Add to dashboard Cite

Electrochemical sensor based on glassy carbon electrode modified by polymelamine formaldehyde/graphene oxide nanocomposite for ultrasensitive detection of oxycodone

et al. 2021

View full text Add to dashboard Cite

A high-throughput bioanalytical assay to support pharmacokinetic interaction study of oxycodone and diazepam in Sprague Dawley rats

Abstract: A high-throughput bioanalytical method for the simulataneous determination of oxycodone and diazepam to support the evaluation of respiratory depression in rats upon co-administration of oxycodone and diazepam.

Cited by 5 publications

References 44 publications

Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat

Effects of sedative psychotropic drugs combined with oxycodone on respiratory depression in the rat

Untitled

Electrochemical sensor based on glassy carbon electrode modified by polymelamine formaldehyde/graphene oxide nanocomposite for ultrasensitive detection of oxycodone

Contact Info

Product

Resources

About