Pharmacology

The Wider Use of Fixed-Dose Combinations Emphasizes the Need for a Global Approach to Regulatory Guideline Development
A fixed-dose combination (FDC) is a drug product in which two or more separate drug components (active pharmaceutical ingredients) are combined in a single-dosage form. Interest in developing FDCs is increasing in a range of diseases. This project investigated the regulatory environment for FDCs in the EU and US. A review of the FDC guidelines set forth by the EMA, FDA, and ICH, followed by int...


Budding yeast as a model to study epigenetics
The budding yeast Saccharomyces cerevisiae has been, and continues to be, one of the most important model systems for biochemical, genetic, and cytologic study of fundamental cellular processes. Its small genome, short generation time, and ease of genetic manipulation have made yeast an ideal model for both sophisticated mechanistic studies and high-throughput screens. Here we focus on the hist...
The anti-epileptic drug substance vigabatrin inhibits taurine transport in intestinal and renal cell culture models
The GABA-mimetic anti-epileptic drug substance vigabatrin is used against infantile spasms. In vitro and in vivo experiments have shown that vigabatrin is transported via the proton coupled amino acid transporter (PAT1) mediating at least parts of the intestinal absorption of the drug. However, such evidence does not preclude the involvement of other transporters. The aim of the present study w...


Inhibitory effects of SKI3246, the rhizome extract of Atractylodes japonica, on visceral hypersensitivity in experimental irritable bowel syndrome rat models
We evaluated the effect of SKI3246, the 50 % ethanol extract of the rhizome of Atractylodes japonica, on visceral hypersensitivity, which is a major characteristic feature of IBS. We used various rat models of visceral hypersensitivity to assess the visceral pain responses to colorectal distension (CRD) in comparison with conventional IBS treatments. Oral administration of SKI3246 dose-depende...
Targeting components of epigenome by small molecules
The diverse epigenetic modifications regulate the gene expression and determine the cellular identity. Pioneering work over the past decades has highlighted that these epigenetic regulations establish normal development but also contribute various diseases. Furthermore, the epigenetic priming events are considered as a key factor for efficient master transcription factor(s) mediated reprogrammi...


The clinical analgesic efficacy of buprenorphine
ObjectiveBased on in vitro assays and select animal models, buprenorphine is commonly called a ‘partial agonist’. An implication is that it should produce less analgesic effect in humans than so-called ‘full agonists’ such as morphine or fentanyl. However, buprenorphine has a multimechanistic pharmacology, and thus partial agonism at a specific receptor is not particularly relevant to i...
‘Selective’ COX-1 or COX-2 NSAIDs: time to change a misleading measure
The ongoing important debate about the relative benefits/risks of COX-1 or COX-2 NSAIDs is hampered by the use of a measure of ‘selectivity’ that is inherently flawed. An alternative measure provides more meaningful and clinically relevant information.

Comparing the life concerns of prescription opioid and heroin users
This study explored life concerns of prescription opioid (PO) and heroin users. Persons entering opioid detoxification rated their level of concern about 43 health and welfare items. Using exploratory factor analysis and conceptual rationale, we identified ten areas of concern. Participants (n=529) were 69.9% male, 87.5% non-Hispanic Caucasian, and 24.2% PO users. Concern about drug problems wa...
A Therapeutic Workplace for the Long-Term Treatment of Drug Addiction and Unemployment: Eight-Year Outcomes of a Social Business Intervention
This study evaluated the long-term effects of a Therapeutic Workplace social business on drug abstinence and employment. Pregnant and postpartum women (N=40) enrolled in methadone treatment were randomly assigned to a Therapeutic Workplace or Usual Care Control group. Therapeutic Workplace participants could work weekdays in training and then as employees of a social business, but were required...

The effect of cognitive functioning on treatment attendance and adherence in comorbid bipolar disorder and cocaine dependence
Although bipolar disorder and substance dependence are both associated with treatment non-adherence and cognitive impairment, no studies have investigated relationships between treatment adherence and cognitive functioning in this population. As part of a clinical trial, baseline performance on two neuropsychological tests in 120 outpatients with bipolar disorder and cocaine dependence was used...
An Assessment of Individual-Level Factors Associated with Alcohol Treatment Utilization among Mexican Americans
The purpose of this study is to identify enabling factors for treatment utilization for alcohol-related problems, and to evaluate how enabling factors vary by need for treatment, among two samples of Mexican American adults. These two distinct samples included 2,595 current and former drinkers (one sample included 787 U. S./Mexico border residents; the other sample included 740 Mexican American...

Do Improvements in Substance Use and Mental Health Symptoms During Treatment Translate to Long-Term Outcomes In The Opposite Domain?
Providers who treat adolescents with co-occurring substance use and mental health issues may prioritize treatment of one set of symptoms believing that improvements in one domain will results in improvements of the other. However, limited empirical data for adolescents provides evidence of such “spillover effects.” Using data from 2900 youth in outpatient treatment, we examined whether duri...
Web-based Training for Primary Care Providers on Screening, Brief Intervention, and Referral to Treatment (SBIRT) for Alcohol, Tobacco, and Other Drugs
This project evaluated a web-based multimedia training for primary care providers in screening, brief intervention, and referral to treatment (SBIRT) for unhealthy use of alcohol, tobacco, and other drugs. Physicians (n=37), physician assistants (n=35), and nurse practitioners (n=20) were recruited nationally by email and randomly assigned to online access to either the multimedia training or c...
The Influence of Treatment Attendance on Subsequent Aggression among Severely Mentally Ill Substance Abusers
The interrelationships between severe mental illness, substance use, and aggression are of longstanding importance with implications for community treatment programs, treatment research and public policy. Through the analysis of longitudinal data collected from 278 patients over a 6-month period following admission to an outpatient dual diagnosis treatment program, this study examined the assoc...
The clustering of psychopathology among adults seeking treatment for alcohol and drug addiction
Beyond the high prevalence of co-occurring mental and substance use disorders, little is known about more complex patterns of psychopathology and multimorbidity, particularly in treatment populations. We sought to identify a parsimonious set of latent classes to describe the structure of mental disorder comorbidity among adults entering outpatient addiction treatment, and explore differences in...