Showing papers by "Purdue Pharma published in 2009"

Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans

Abstract: Interindividual variability in response to chemicals and drugs is a common regulatory concern. It is assumed that xenobiotic-induced adverse reactions have a strong genetic basis, but many mechanism-based investigations have not been successful in identifying susceptible individuals. While recent advances in pharmacogenetics of adverse drug reactions show promise, the small size of the populations susceptible to important adverse events limits the utility of whole-genome association studies conducted entirely in humans. We present a strategy to identify genetic polymorphisms that may underlie susceptibility to adverse drug reactions. First, in a cohort of healthy adults who received the maximum recommended dose of acetaminophen (4 g/d x 7 d), we confirm that about one third of subjects develop elevations in serum alanine aminotransferase, indicative of liver injury. To identify the genetic basis for this susceptibility, a panel of 36 inbred mouse strains was used to model genetic diversity. Mice were treated with 300 mg/kg or a range of additional acetaminophen doses, and the extent of liver injury was quantified. We then employed whole-genome association analysis and targeted sequencing to determine that polymorphisms in Ly86, Cd44, Cd59a, and Capn8 correlate strongly with liver injury and demonstrated that dose-curves vary with background. Finally, we demonstrated that variation in the orthologous human gene, CD44, is associated with susceptibility to acetaminophen in two independent cohorts. Our results indicate a role for CD44 in modulation of susceptibility to acetaminophen hepatotoxicity. These studies demonstrate that a diverse mouse population can be used to understand and predict adverse toxicity in heterogeneous human populations through guided resequencing.

Pharmaceutical dosage forms comprising poly(e-caprolactone)

Abstract: The present invention relates to pharmaceutical dosage forms, for example to pharmaceutical dosage forms comprising poly(e-caprolactone), and processes of manufacture, uses, and methods of treatment thereof

Substituted-quinoxaline-type bridged-piperidine compounds and the uses thereof

Abstract: The invention relates to Substituted--Quinoxaline-Type Bridged-Piperidine Compounds, compositions comprising an effective amount of a Substituted-Quinoxaline- Type Bridged-Piperidine Compound and methods to treat or prevent a condition, such as pain, comprising administering to an animal in need thereof an effective amount of a Sub-stituted-Quinoxaline-Type Bridged-Piperidine Compound.

Monocyclic compounds and their use as TRPV1 ligands

Abstract: The invention relates to compounds of formula I and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof.

RxPATROL: A Web-based tool for combating pharmacy theft

Abstract: Objective To report the incidence of pharmacy-related burglaries and robberies and characteristics of pharmacies where such crimes have occurred using recent data from Rx Pattern Analysis Tracking Robberies & Other Losses (RxPATROL), a national Web-based information clearinghouse on pharmacy-related theft of prescription medications and over-the-counter products. Design Descriptive, nonexperimental study. Setting United States between 2005 and 2006. Participants Not applicable. Interventions Not applicable. Main outcome measures Number of pharmacy theft reports received; incident type, date, and location; point of entry; and pharmacy security features. Results Between 2005 and 2006, 202 pharmacy burglary and 299 pharmacy robbery reports from 45 different states were filed with RxPATROL. More than 70% of pharmacies reporting such crimes lacked a security camera. Among those reporting a burglary, 60% lacked dead bolt locks, a solid exterior door, a motion detector device, or a safe or vault for storage of controlled substances. Burglars most often obtained access to the pharmacy via the front door. Conclusion RxPATROL is a Web-based tool that can assist pharmacies and law enforcement in collaborating more effectively to combat and prevent pharmacy-related crimes.

Bicycloheteroaryl compounds and their use as TRPV1 ligands

Abstract: The invention relates to compounds of formula I and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of formula I or a pharmaceutically acceptable derivative thereof.

Tetrahydropyridinyl and dihydropyrrolyl compounds and the use thereof

Abstract: The invention relates to tetrahydropyridinyl and dihydropyrrolyl compounds of Formula (I): and pharmaceutically acceptable salts, prodrugs, or solvates thereof, wherein X, Y, Z, R1, R2, m, and n are defined as set forth in the specification. The invention is also directed to the use of compounds of Formula (I) to treat a disorder responsive to the blockade of calcium channels, and particularly N-type calcium channels. Compounds of the present invention are especially useful for treating pain.

Heterocyclic TRPV1 receptor ligands

Abstract: The invention relates to compounds of formulae I(a)-I(d): and pharmaceutically acceptable derivatives thereof, compositions comprising an effective amount of a compound of formulae I(a)-I(d) or a pharmaceutically acceptable derivative thereof, and methods for treating or preventing a condition such as pain, UI, an ulcer, IBD and IBS, comprising administering to an animal in need thereof an effective amount of a compound of formulae I(a)-I(d) or a pharmaceutically acceptable derivative thereof.

Compounds comprising heterocyclic-substituted piperidine for treating pain

Abstract: The invention relates to Heterocyclic-Substituted Piperidine Compounds, compositions comprising an effective amount of a Heterocyclic-Substituted Piperidine Compound and methods to treat or prevent a condition, such as pain, comprising administering to an animal in need thereof an effective amount of a Heterocyclic-Substituted Piperidine Compound.

Proline analogs as ligands for cannabinoid receptors

Abstract: The present invention relates to Proline Analog Compounds that are ligands for cannabinoid receptors, compositions comprising a Proline Analog Compound and a pharmaceutically-acceptable carrier, methods of making such Proline Analog Compounds, and methods for treating or preventing a Condition comprising administering an effective amount of a Proline Analog Compound to an animal in need thereof.

Proline analogs as ligands for cannabinoid receptors for the treatment of pain

Abstract: The present invention relates to Proline Analog Compounds that are ligands for cannabinoid receptors, compositions comprising a Proline Analog Compound and a pharmaceutically-acceptable carrier, methods of making such Proline Analog Compounds, and methods for treating or preventing a Condition comprising administering an effective amount of a Proline Analog Compound to an animal in need thereof.

Nanostructures with High Load of Active Agents

Abstract: The present invention provides an improved method of loading silica nanostructures with an active agent, comprising exposing a mixture comprising a liquid medium containing an active agent and silica nanostructures to reduced air pressure for a time period, and then returning the mixture to atmospheric air pressure at the end of the time period