Medicine and Health Sciences Commons^™

Pharmacokinetic Study Of Intranasal Dexamethasone And Methylprednisolone Compared With Intravenous Administration: Two Open-Label, Single-Dose, Two-Period, Two-Sequence, Cross-Over Study In Healthy Volunteers, Graciela Cárdenas, Raúl J. Bobes, Gladis Fragoso, Nicolas I. Pérez-Osorio, Marisela Hernández, Alejandro Espinosa, Agnes Fleury, José Flores, Juan Carlos Alvarenga, Juan Pedro Laclette

School of Medicine Publications and Presentations

Dexamethasone (DXM) and methylprednisolone (MEP) are potent glucocorticoids used to control several inflammatory conditions. Evidence of delayed DXM reaching the central nervous system (CNS) as well as tachyphylaxis and systemic, undesirable side effects are the main limitations of peripheral delivery. Intranasal administration offers direct access to the brain as it bypasses the blood–brain barrier. The Mucosal Atomization Device is an optimal tool that can achieve rapid absorption into the CNS and the bloodstream across mucosal membranes. This study was designed to evaluate and compare the bioavailability of DXM and MEP after intranasal versus intravenous administration. Two open-label, balanced, randomized, two-treatment, …

Pharmacokinetics Of Esomeprazole In Goats (Capra Aegagrus Hircus) After Intravenous And Subcutaneous Administration, Rachel L. Fladung, Joseph Smith, Melissa Hines, Windy Soto-Gonzalez, Bryanna Fayne, Rebecca Rahn, Olivia Escher, Lainey Harvill, Joan Bergman, Jessica Garcia, Amanda Kreuder

Faculty Publications and Other Works -- Large Animal Clinical Sciences

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats.

Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats.

Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. …

Methylone And Mdma Pharmacokinetics Following Controlled Administration In Humans, Lourdes Poyatos, Alfredo Fabrizio Lo Faro, Diletta Berardinelli, Giorgia Sprega, Sara Malaca, Simona Pichini, Marilyn A. Huestis, Esther Papaseit, Clara Pérez-Mañá, Francesco Paolo Busardò, Magí Farré

Institute of Emerging Health Professions Faculty Papers

The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50–200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d5, MDA-d5 and methylone-d3 internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v/v) were then added, mixed well and centrifuged. The supernatant was fortified with …

Pharmacokinetics Of Butorphanol Following Intravenous And Intramuscular Administration In Donkeys: A Preliminary Study, Lisa S. Ebner, Odette O, Bradley Simon, Ignacio Lizarraga, Joseph Smith, Sherry Cox

Faculty Publications and Other Works -- Large Animal Clinical Sciences

The pharmacokinetics of butorphanol after intravenous (IVB) and intramuscular (IMB) administration in donkeys were determined in this preliminary study. Healthy male gelded donkeys (n = 5), aged 6–12 years old, were administered 0.1 mg/kg butorphanol IV or IM in a randomized, crossover design. Blood samples were obtained at predetermined intervals for 24 h (IVB) and 48 h (IMB) after administration. Plasma butorphanol concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters were calculated. Following IVB administration, mean (± SE) apparent volume of distribution, elimination half-life, total body clearance, and area under the plasma concentration time curve from …

Comparative Single Dose Pharmacokinetics And Metabolism Of Racemic Primaquine And Its Enantiomers In Human Volunteers, Washim Khan, Yan Hong Wang, Narayan D. Chaurasiya, Np Dhammika Nanayakkara

Faculty and Student Publications

Primaquine (PQ) is a racemic drug used in treatment of malaria for six decades. Recent studies suggest that the two enantiomers of PQ are differentially metabolized in animals, and this results in different pharmacological and toxicological profiles. The current study characterizes the pharmacokinetic (PK) properties, metabolism and tolerability of the individual enantiomers of PQ in healthy human volunteers with normal glucose-6-phosphate dehydrogenase (G6PD) activity. Two cohorts (at two dose levels), each with 18 subjects, participated in three study arms in a crossover fashion: a single dose of the (−)-R enantiomer (RPQ), a single dose of the (+)-S enantiomer (SPQ), and …

Oral Drug Dosing Following Bariatric Surgery: General Concepts And Specific Dosing Advice, Jurjen S. Kingma, Desirée M. T. Burgers, Valerie M. Monpellier, Marinus J. Wiezer, Heleen J. Blussé Van Oud‐Alblas, Janelle D. Vaughns, Catherine M. T. Sherwin, Catherijne A. J. Knibbe

Pediatrics Faculty Publications

Bariatric or weight-loss surgery is a popular option for weight reduction. Depending on the surgical procedure, gastric changes like decreased transit time and volume and increased pH, decreased absorption surface in the small intestine, decreased exposure to bile acids and enterohepatic circulation, and decreased gastrointestinal transit time may be expected. In the years after bariatric surgery, patients will also substantially lose weight. As a result of these changes, the absorption, distribution, metabolism and/or elimination of drugs may be altered. The purpose of this article is to report the general influence of bariatric surgery on oral drug absorption, and to provide …

Risk Of Opioid Overdose Associated With Concomitant Use Of Oxycodone And Selective Serotonin Reuptake Inhibitors, Ismaeel Yunusa, Joshua J. Gagne, Kazuki Yoshida, Katsiaryna Bykov

Faculty Publications

Importance Some selective serotonin reuptake inhibitors (SSRIs) inhibit the enzymes responsible for the metabolism of oxycodone, a potent prescription opioid. The clinical consequences of this interaction on the risk of opioid overdose have not been elucidated.

Objective To compare opioid overdose rates in patients initiating oxycodone while taking SSRIs that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) vs SSRIs that are not.

Design, Setting, and Participants This cohort study included adults who initiated oxycodone while receiving SSRI therapy between 2000 and 2020 whose data were included in 3 US health insurance databases.

Exposures Use of SSRIs that strongly …

A Semi-Physiological Three-Compartment Model Describes Brain Uptake Clearance And Efflux Of Sucrose And Mannitol After Iv Injection In Awake Mice, Behnam Noorani, Ekram Ahmed Chowdhury, Faleh Alqahtani, Md Sanaullah Sajib, Yeseul Ahn, Ehsan Nozohouri, Dhavalkumar Patel, Constantinos Mikelis, Reza Mehvar, Ulrich Bickel

Pharmacy Faculty Articles and Research

Purpose

To evaluate a three-compartmental semi-physiological model for analysis of uptake clearance and efflux from brain tissue of the hydrophilic markers sucrose and mannitol, compared to non-compartmental techniques presuming unidirectional uptake.

Methods

Stable isotope-labeled [¹³C]sucrose and [¹³C]mannitol (10 mg/kg each) were injected as IV bolus into the tail vein of awake young adult mice. Blood and brain samples were taken after different time intervals up to 8 h. Plasma and brain concentrations were quantified by UPLC-MS/MS. Brain uptake clearance (K_in) was analyzed using either the single-time point analysis, the multiple time point graphical method, …

Race And Sex Associations With Tacrolimus Pharmacokinetics In Stable Kidney Transplant Recipients, Kathleen M. Tornatore, Calvin J. Meaney, Kristopher Attwood, Daniel A. Brazeau, Gregory E. Wilding, Joseph D. Consiglio, Aijaz Gundroo, Shrley S. Chang, Vanessa Gray, Louise M. Cooper, Rocco C. Venuto

Pharmaceutical Science and Research

Study Objective: This study investigated race and sex differences in tacrolimus pharmacokinetics and pharmacodynamics in stable kidney transplant recipients.

Design and Setting: A cross-sectional, open-label, single center, 12-h pharmacokinetic-pharmacodynamic study was conducted. Tacrolimus pharmacokinetic parameters included area under the concentration-time curve (AUC_0–12), AUC_0–4, 12-h troughs (C_{12 h}), maximum concentrations (C_max), oral clearance (Cl), with dose-normalized AUC_0–12, troughs, and C_max with standardized adverse effect scores. Statistical models were used to analyze end points with individual covariate-adjustment including clinical factors, genotypic variants CYP3A5*3, CYP3A5*6, CYP3A5*7(CYP3A5*3*6*7 …