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

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 (pCO ).

Novel simultaneous method for the determination of avobenzone and oxybenzone in human plasma by UHPLC-MS/MS with phospholipid removal pretreatment: An application to a sunscreen clinical trial.

Application of sunscreen is one of many ways to protect skin from the harmful effects of UV radiation. Sunscreen products are widely used and regulated as over-the-counter drug products in the United States. The U.

Developing an animal model to detect drug-drug interactions impacting drug-induced respiratory depression.

Opioids and benzodiazepines were frequently co-prescribed to patients with pain and psychiatric or neurological disorders; however, co-prescription of these drugs increased the risk for severe respiratory depression and death. Consequently, the U.S.

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

Benzodiazepines potentiate respiratory depression when combined with an opioid leading the U.S Food and Drug Administration (FDA) to recommend updating the labels of these products with a boxed warning for respiratory depression with co-use. Potential respiratory depression upon co-administration of opioids with some psychotropic drugs is not well understood.

Novel High-Throughput Quantitation of Potent hERG Blocker Dofetilide in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Application in a Phase 1 ECG Biomarker Validation Study.

The authors developed a novel, sensitive high-throughput ultra-performance liquid chromatography-tandem mass spectrometric method for the determination of dofetilide in human plasma. To compensate for the matrix effect, a deuterated internal standard was used. The method employed a very low sample volume (50 μL) of plasma for sample processing by using simple protein precipitation extraction in a 96-well plate.

Application of Mechanistic Ocular Absorption Modeling and Simulation to Understand the Impact of Formulation Properties on Ophthalmic Bioavailability in Rabbits: a Case Study Using Dexamethasone Suspension.

Developing mathematical models to predict changes in ocular bioavailability and pharmacokinetics due to differences in the physicochemical properties of complex topical ophthalmic suspension formulations is important in drug product development and regulatory assessment. Herein, we used published FDA clinical pharmacology review data, in-house, and literature rabbit pharmacokinetic data generated for dexamethasone ophthalmic suspensions to demonstrate how the mechanistic Ocular Compartmental Absorption and Transit model by GastroPlus™ can be used to characterize ocular drug pharmacokinetic performance in rabbits for suspension formulations. This model was used to describe the dose-dependent (0.

An alternating polarity switching assay for quantification of oxycodone and topiramate: An application of LC-MS/MS method in support to PK/PD study in rodents.

In mass spectrometry, compounds that have different ionization properties experience challenges in simultaneous analysis. In the present paper, the authors proposed a polarity switching (+ve and -ve) LC-MS/MS method to analyze oxycodone and topiramate in a single run. The developed method was validated in the range of 5-1000 ng/mL for oxycodone and 20-5000 ng/mL for topiramate as per the US FDA guidelines.

Determination of Non-Transferrin Bound Iron, Transferrin Bound Iron, Drug Bound Iron and Total Iron in Serum in a Rats after IV Administration of Sodium Ferric Gluconate Complex by Simple Ultrafiltration Inductively Coupled Plasma Mass Spectrometric Detection.

A rapid, sensitive and specific ultrafiltration inductively-coupled plasma mass spectrometry (UF-ICP-MSICP-MS) method was developed and validated for the quantification of non-transferrin bound iron (NTBI), transferrin bound iron (TBI), drug bound iron (DI) and total iron (TI) in the same rat serum sample after intravenous (IV) administration of iron gluconate nanoparticles in sucrose solution (Ferrlecit). Ultrafiltration with a 30 kDa molecular cut-off filter was used for sample cleanup. Different elution solvents were used to separate each form of iron from sample serum.

Paraquat exposure and Sod2 knockdown have dissimilar impacts on the Drosophila melanogaster carbonylated protein proteome.

Exposure to Paraquat and RNA interference knockdown of mitochondrial superoxide dismutase (Sod2) are known to result in significant lifespan reduction, locomotor dysfunction, and mitochondrial degeneration in Drosophila melanogaster. Both perturbations increase the flux of the progenitor ROS, superoxide, but the molecular underpinnings of the resulting phenotypes are poorly understood. Improved understanding of such processes could lead to advances in the treatment of numerous age-related disorders.