Trends in Research and Graduate Programs in Schools and Colleges of Pharmacy, Part 1: Programs.

To examine the landscape of research and graduate education nationally and within schools and colleges of pharmacy. This report is part 1 of a three-part series and focuses on graduate programs' research funding and science faculty composition and diversity. Between FY2008 and FY2017, the number of full-time faculty members in schools and colleges of pharmacy increased 36%.

Trends in Research and Graduate Affairs in Schools and Colleges of Pharmacy, Part 2: Students.

To examine the landscape of research and graduate affairs nationally and within schools and colleges of pharmacy. This report, part 2 of a three-part series, focuses on characteristics of full-time PhD enrollees and graduates in schools and colleges of pharmacy, and career planning and preparation in graduate programs. Despite a 41% increase in funding awarded by the National Institutes of Health (NIH) to schools and colleges of pharmacy over the last 10 years, NIH funding per principal investigator only increased 14% and graduate student enrollment increased just 6% during the period.

Trends in Research and Graduate Affairs in Schools and Colleges of Pharmacy, Part 3: Underrepresented Minorities.

To examine the landscape of research and graduate affairs nationally and within schools and colleges of pharmacy. This report, part 3 of a three-part series, focuses on underrepresented minority (URM) faculty members and students, with a focus on recruitment and retention. There has been a substantial increase in recruitment of Asian faculty members by schools of pharmacy over the last 10 years, but there has been only minimal changes in the numbers of Black and Hispanic faculty numbers, which reflects the challenges in recruitment and retention of URM faculty members.

Randomised trial of azithromycin to eradicate in preterm infants.

Objective: To test whether azithromycin eradicates from the respiratory tract in preterm infants.

Design: Prospective, phase IIb randomised, double-blind, placebo-controlled trial.

Setting: Seven level III-IV US, academic, neonatal intensive care units (NICUs).

Pharmapreneur - Defining a Framework for Entrepreneurship in Pharmacy Education.

To determine the role of entrepreneurism within the broader missions of schools of pharmacy and develop an educational framework to produce pharmacist entrepreneurs. Following a systematic review and six semi-structured interviews, a three-round Delphi process was conducted with an expert panel comprised of successful entrepreneurs, pharmacy faculty members and administrators, students, and community members. Participants were asked about the role of entrepreneurship in a pharmacy school's mission, how they would define a pharmacist entrepreneur, and to identify the knowledge, skills, and attitudes (KSAs) expected to be successful as a pharmacist entrepreneur.

A Systematic Review of Entrepreneurship in Pharmacy Practice and Education.

To review literature pertaining to entrepreneurship in pharmacy practice, education, and the knowledge, skills, and attitudes (KSAs) identified for pharmacist entrepreneurs. In terms of pharmacy practice, entrepreneurship was most frequently identified with innovation and creativity to develop new opportunities for pharmacists. The most frequent role for entrepreneurship in pharmacy education was related to schools putting a greater emphasis on innovation, creativity, or divergent thinking.

Trends in the Pharmacist Workforce and Pharmacy Education.

This commentary is an observation of longitudinal trends in national data on the pharmacist workforce and pharmacy education. Data indicate seismic shifts in supply and demand, from critical shortage to imminent oversupply. The change in the profession to employing more patient-care focused jobs has been observed as slow and minimal, although academia has focused on the clinical training and rapidly increased enrollments.

Pharmacokinetics, microbial response, and pulmonary outcomes of multidose intravenous azithromycin in preterm infants at risk for Ureaplasma respiratory colonization.

The study objectives were to refine the population pharmacokinetics (PK) model, determine microbial clearance, and assess short-term pulmonary outcomes of multiple-dose azithromycin treatment in preterm infants at risk for Ureaplasma respiratory colonization. Fifteen subjects (7 of whom were Ureaplasma positive) received intravenous azithromycin at 20 mg/kg of body weight every 24 h for 3 doses. Azithromycin concentrations were determined in plasma samples obtained up to 168 h post-first dose by using a validated liquid chromatography-tandem mass spectrometry method.

Opioids and efflux transporters. Part 4: influence of N-substitution on P-glycoprotein substrate activity of noroxymorphone analogues.

The efflux transporter protein P-glycoprotein (P-gp) is capable of affecting the central distribution of diverse neurotherapeutics, including opioid analgesics, through their active removal from the brain. P-gp located at the blood brain barrier has been implicated in the development of tolerance to opioids and demonstrated to be up-regulated in rats tolerant to morphine and oxycodone. We have previously examined the influence of hydrogen-bonding oxo-substitutents on the P-gp-mediated efflux of 4,5-epoxymorphinan analgesics, as well as that of N-substituted analogues of meperidine.

Induction of xenobiotic receptors, transporters, and drug metabolizing enzymes by oxycodone.

Perturbations of the expression of transporters and drug-metabolizing enzymes (DMEs) by opioids can be the locus of deleterious drug-drug interactions (DDIs). Many transporters and DMEs are regulated by xenobiotic receptors [XRs; e.g.

Azithromycin to prevent bronchopulmonary dysplasia in ureaplasma-infected preterm infants: pharmacokinetics, safety, microbial response, and clinical outcomes with a 20-milligram-per-kilogram single intravenous dose.

Ureaplasma respiratory tract colonization is associated with bronchopulmonary dysplasia (BPD) in preterm infants. Previously, we demonstrated that a single intravenous (i.v.

The impact of AT1002 on the delivery of ritonavir in the presence of bioadhesive polymer, carrageenan.

New insights into the modification of the tight junctions theoretically offer the opportunity to regulate the diffusion barrier and then make it possible to investigate a permeation enhancer of low-bioavailability therapeutic agents. AT1002, a minimum biologically active fragment of zonula occludens toxin which reversibly opens intercellular tight junctions after binding to the Zonulin receptor, increased the transport of various molecular weight markers or low-bioavailability agents. The objective of this study was continuously to evaluate the permeation-enhancing ability of AT1002 in the presence of the bioadhesive agent, carrageenan after intranasal administration of the antiretroviral drug, ritonavir, and the permeation enhancement ratio compared with the previous results.

Enaminones 12. An explanation of anticonvulsant activity and toxicity per Linus Pauling's clathrate hypothesis.

The x-ray crystal structure of 3-((5-methylisoxazol-3-yl)amino)-5-methylcyclohex-2-enone (12b) and 3-((5-methylisoxazolyl-3-yl)amino)-5,5-dimethylcyclohex-2-enone (12c) were determined and correlated to their anticonvulsant activity in mice and rats. A hypothesis for the toxicity of the analogs are advanced. In addition, a series of 5-methyl-N-(3-oxocyclohex-1-enyl)-isoxazole-3-carboxamides were synthesized and evaluated for anticonvulsant activity.

The influence of stabilizer and bioadhesive polymer on the permeation-enhancing effect of AT1002 in the nasal delivery of a paracellular marker.

Permeation enhancers are of major interest to improve the low bioavailability of therapeutic agents due to poor membrane permeation. AT1002, a six-amino acid fragment of Zonula occludens toxin, was reported to possess permeation-enhancing effects. However, further studies were suggested to focus on the peptide nature of AT1002 like stability and membrane clearance to accurately reflect its permeation-enhancing potential.

The influence of AT1002 on the nasal absorption of molecular weight markers and therapeutic agents when co-administered with bioadhesive polymers and an AT1002 antagonist, AT1001.

Objectives: The purpose of this study was to demonstrate the effects of the tight junction permeation enhancer, AT1002, on the nasal absorption of molecular weight markers and low bioavailable therapeutic agents co-administered with bioadhesive polymers or zonulin antagonist.

Methods: The bioadhesive polymers, carrageenan and Na-CMC, were prepared with AT1002 to examine the permeation-enhancing effect of AT1002 on the nasal absorption of inulin, calcitonin and saquinavir after nasal administration to Sprague-Dawley rats. Blood samples were collected over a 6-hour period from a jugular cannula.

Increased oxidative-modifications of cytosolic proteins in 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)-exposed rat liver.

It is well established that 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) causes acute liver damage in animals and humans. The aim of this study was to identify and characterize oxidative modification and inactivation of cytosolic proteins in MDMA-exposed rats. Markedly increased levels of oxidized and nitrated cytosolic proteins were detected 12 h after the second administration of two consecutive MDMA doses (10 mg/kg each).

Pharmacokinetics, safety, and biologic effects of azithromycin in extremely preterm infants at risk for ureaplasma colonization and bronchopulmonary dysplasia.

Ureaplasma spp. respiratory tract colonization is a significant risk factor for bronchopulmonary dysplasia (BPD), a chronic lung disorder in preterm infants. As an initial step preparatory to future clinical trials to evaluate the clinical efficacy of azithromycin to prevent BPD, the authors characterized the pharmacokinetics, safety, and biological effects of a single intravenous dose of azithromycin (10 mg/kg) in preterm neonates (n = 12) 24 to 28 weeks gestation at risk for Ureaplasma infection and BPD.

Differential activation of pregnane X receptor and constitutive androstane receptor by buprenorphine in primary human hepatocytes and HepG2 cells.

Buprenorphine is a partial μ-opioid receptor agonist used for the treatment of opioid dependence that has several advantages over methadone. The principal route of buprenorphine disposition has been well established; however, little is known regarding the potential for buprenorphine to influence the metabolism and clearance of other drugs by affecting the expression of drug-metabolizing enzymes (DMEs). Here, we investigate the effects of buprenorphine on the activation of pregnane X receptor (PXR) and constitutive androstane receptor (CAR), as well as the induction of DMEs, in both HepG2 cells and human primary hepatocytes (HPHs).

Repeated administration of oxycodone modifies the gene expression of several drug metabolising enzymes in the hepatic tissue of male Sprague-Dawley rats, including glutathione S-transferase A-5 (rGSTA5) and CYP3A2.

Objectives: Clinical use and illicit abuse of the potent opioid agonist oxycodone has dramatically increased over the past decade. Yet oxycodone remains one of the least studied opioids, particularly its interactions on the genomic level. The aim of this study was to examine potential alterations in gene expression of drug metabolising enzymes in the liver tissue of male Sprague-Dawley rats chronically treated with oxycodone.

Mechanisms of MDMA (ecstasy)-induced oxidative stress, mitochondrial dysfunction, and organ damage.

Despite numerous reports about the acute and sub-chronic toxicities caused by MDMA (3,4-methylenedioxymethamphetamine, ecstasy), the underlying mechanism of organ damage is poorly understood. The aim of this review is to present an update of the mechanistic studies on MDMA-mediated organ damage partly caused by increased oxidative/nitrosative stress. Because of the extensive reviews on MDMA-mediated oxidative stress and tissue damage, we specifically focus on the mechanisms and consequences of oxidative-modifications of mitochondrial proteins, leading to mitochondrial dysfunction.

Characterization of the transport, metabolism, and pharmacokinetics of the dopamine D3 receptor-selective fluorenyl- and 2-pyridylphenyl amides developed for treatment of psychostimulant abuse.

The recent discovery of novel high-affinity and selective dopamine D3 receptor (DA D3R) antagonists and partial agonists has provided tools with which to further elucidate the role DA D3R plays in substance abuse. The present study was conducted to evaluate the transport, metabolism, pharmacokinetics, and brain uptake of the DA D3R-selective fluorenyl amides, NGB 2904 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-9H-fluorene-2-carboxamide] fumarate) and JJC 4-077 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-3-hydroxybutyl)-9H-fluorene-2-carboxamide hydrochloride], and the 2-pyridylphenyl amides, CJB 090 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)-4-(pyridine-2-yl)benzamide hydrochloride] and PG 01037 [N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)-trans-but-2-enyl)-4-(pyridine-2-yl)benzamide hydrochloride], all of which have been studied in animal models of psychostimulant abuse. Additional screening with a panel of human and rat Supersomes was performed for NGB 2904 and PG 01037.

The ethanol metabolite acetaldehyde increases paracellular drug permeability in vitro and oral bioavailability in vivo.

Alcohol consumption leads to the production of the highly reactive ethanol metabolite, acetaldehyde, which may affect intestinal tight junctions and increase paracellular permeability. We examined the effects of elevated acetaldehyde within the gastrointestinal tract on the permeability and bioavailability of hydrophilic markers and drug molecules of variable molecular weight and geometry. In vitro permeability was measured unidirectionally in Caco-2 and MDCKII cell models in the presence of acetaldehyde, ethanol, or disulfiram, an aldehyde dehydrogenase inhibitor, which causes acetaldehyde formation when coadministered with ethanol in vivo.