Insilico Screening of Pentacyclic Triterpenoids against Vascular Dementia Target's.

Vascular dementia (VaD) accounts to 30% of cases and is predicted as second most common form of dementia after Alzheimer's disease by WHO. Earlier studies reported that plant-derived pentacyclic triterpenoids possess a wide range of pharmacological activities but these compounds are not extensively studied for their neuroprotective potential against VaD. This in silico approach was designed to screen 20 pentacyclic triterpenoid plant compounds against known targets of VaD using Flare software.

3D QSAR based Virtual Screening of Flavonoids as Acetylcholinesterase Inhibitors.

In an attempt to develop therapeutic agents to treat Alzheimer's disease, a series of flavonoid analogues were collected, which already had established acetylcholinesterase (AChE) enzyme inhibition activity. For each molecule we also collected biological activity data (Ki). Then, 3D-QSAR (quantitative structure-activity relationship model) was developed which showed acceptable predictive and descriptive capability as represented by standard statistical parameters r2 and q2.

Pharmacokinetics/pharmacodynamics of L-ornithine phenylacetate in overt hepatic encephalopathy and the effect of plasma ammonia concentration reduction on clinical outcomes.

Hepatic encephalopathy (HE) is a serious neurocognitive complication of liver dysfunction, often associated with elevated plasma ammonia. Ornithine phenylacetate (OP), a potent ammonia scavenger, is being evaluated for the treatment of acute/overt HE. The pharmacokinetics and pharmacodynamics of OP in patients with HE were characterized in this phase IIb study (NCT01966419).

In Silico and In Vivo Studies on Quercetin as Potential Anti-Parkinson Agent.

Parkinson's disease (PD) is a major cause of morbidity and mortality among older individuals. Several researchers have suggested that iron chelators which cross the blood-brain barrier (BBB) might have clinical efficacy in treating PD. Therefore, efforts are made not only in order to improve the effect of L-dopa but also to introduce drugs which provide anti-parkinsonian and neuroprotective effects.

Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants.

Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patients with acute postoperative pain assessed pharmacokinetics (PK) and safety, in addition to efficacy and pharmacodynamics of repeated doses administered over 24 hours. Neonate and infant patients (<2 years of age) who were undergoing surgery or had experienced a traumatic injury and were expected to need pain management for at least 24 hours were enrolled.

In vitro binding and receptor-mediated activity of terlipressin at vasopressin receptors V and V.

Terlipressin, a synthetic, systemic vasoconstrictor with selective activity at vasopressin-1 (V) receptors, is a pro-drug for the endogenous/natural porcine hormone [Lys]-vasopressin (LVP). We investigated binding and receptor-mediated cellular activities of terlipressin, LVP, and endogenous human hormone [Arg]-vasopressin (AVP) at V and vasopressin-2 (V) receptors. Cell membrane homogenates of Chinese hamster ovary cells expressing human V and V receptors were used in competitive binding assays to measure receptor-binding activity.

Pharmacokinetics of Oral and Intravenous Paracetamol (Acetaminophen) When Co-Administered with Intravenous Morphine in Healthy Adult Subjects.

Background And Objective: Several features favor paracetamol (acetaminophen) administration by the intravenous rather than the oral route in the postoperative setting. This study compared the pharmacokinetics and bioavailability of oral and intravenous paracetamol when given with or without an opioid, morphine.

Methods: In this randomized, single-blind, parallel, repeat-dose study in healthy adults, subjects received four repeat doses of oral or intravenous 1000 mg paracetamol at 6-h intervals, and morphine infusions (0.

Single-dose pharmacokinetics of 2 or 3 tablets of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) under fed and fasted conditions: two randomized open-label trials.

Background: Biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) 7.5/325-mg tablets are formulated with gastroretentive ER drug delivery technology that has been associated with clinically meaningful food effects in other approved products. Two phase 1 studies evaluated potential effects of food on single-dose pharmacokinetics of IR/ER HB/APAP tablets.

Single- and multiple-dose pharmacokinetics of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) compared with immediate-release hydrocodone bitartrate/ibuprofen and immediate-release tramadol HCl/acetaminophen.

Objective: To characterize the single-dose and steady-state pharmacokinetics (PK) of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (IR/ER HB/APAP), IR HB/ibuprofen, and IR tramadol HCl/APAP.

Methods: In this single-center, open-label, randomized, four-period crossover study, healthy participants received four treatments under fasted conditions: 1) a single dose of two IR/ER HB/APAP 7.5/325 mg tablets (15/650 mg total dose) on day 1, followed by two tablets every 12 hours (q12h) beginning on day 3; 2) a single dose of IR HB/ibuprofen 15/400 mg (divided as one 7.

Comparison of single-dose and multiple-dose pharmacokinetics between two formulations of hydrocodone bitartrate/acetaminophen: immediate-release versus biphasic immediate-release/extended release.

Objective: This study aimed to compare the single-dose and steady-state pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) and IR HB/APAP.

Setting: The study was conducted in a contract research center.

Participants: The study included healthy adults.

Pooled post hoc analysis of population pharmacokinetics of oxycodone and acetaminophen following a single oral dose of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

This analysis evaluated the single-dose population pharmacokinetics (PK) of biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325 mg tablets administered under fasted conditions and the effects of a meal on their single-dose population PK. Data were pooled from four randomized, single-dose crossover trials enrolling healthy adult (18-55 years old) participants (three trials) and nondependent recreational users of prescription opioids (one trial) with a body weight of ≥59 kg.

Correlation of Subjective Effects with Systemic Opioid Exposure from Fixed-Dose Combinations of Oxycodone/Acetaminophen in Recreational Users of Prescription Drugs.

Objective: To correlate abuse-related pharmacodynamic measures and pharmacokinetic measures after administering immediate-release/extended-release and immediate-release oxycodone/acetaminophen fixed-dose combination analgesicsDesign. Randomized, double-blind, active- and placebo-controlled, 7-way crossover studySetting. Contract research organizationSubjects.

Frog intestinal perfusion to evaluate drug permeability: application to p-gp and cyp3a4 substrates.

To evaluate the reliability of using in situ frog intestinal perfusion technique for permeability assessment of carrier transported drugs which are also substrates for CYP enzymes. Single Pass Intestinal Perfusion (SPIP) studies were performed in frogs of the species Rana tigrina using established method for rats with some modifications after inducing anesthesia. Effective permeability coefficient (P eff) of losartan and midazolam was calculated in the presence and absence of inhibitors using the parallel-tube model.

Pooled Post Hoc Analysis of Population Pharmacokinetics of Oxycodone and Acetaminophen Following Multiple Oral Doses of Biphasic Immediate-Release/Extended-Release Oxycodone/Acetaminophen Tablets.

Objective: To examine whether biphasic immediate-release (IR)/extended-release (ER) oxycodone (OC)/acetaminophen (APAP) 7.5/325-mg tablets have clinically relevant variability in population pharmacokinetics (PK).

Design: Post hoc analysis of 2 phase 1 randomized, open-label, multiple-dose crossover studies.

Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

Context: Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release.

Objective: To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets.

Materials And Methods: IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving.

Human abuse potential of immediate-release/extended-release versus immediate-release hydrocodone bitartrate/acetaminophen: a randomized controlled trial in recreational users of prescription opioids.

Background: The abuse potential of prescription opioids is well established. This study compared positive, subjective drug effects of single, equal doses of biphasic immediate release (IR)/extended release (ER) hydrocodone bitartrate (HB)/acetaminophen (acetyl-p-aminophenol [APAP]) 7.5/325 mg tablets versus IR HB/APAP 7.

Pharmacokinetics and bioavailability of oxycodone and acetaminophen following single-dose administration of MNK-795, a dual-layer biphasic IR/ER combination formulation, under fed and fasted conditions.

Background: XARTEMIS™ XR (formerly MNK-795) is a combination oxycodone (OC) and acetaminophen (APAP) analgesic with both immediate-release and extended-release (ER) components (ER OC/APAP). The tablets are designed with gastric-retentive ER oral delivery technology that releases the ER component at a controlled rate in the upper gastrointestinal tract. Because consumption of food has demonstrated an impact on the pharmacokinetics (PK) of some marketed products using gastric-retentive ER oral delivery technology, a characterization of the effects of fed (high- and low-fat diets) versus fasted conditions on the PK of ER OC/APAP was performed.

Comparison of subjective effects of extended-release versus immediate-release oxycodone/acetaminophen tablets in healthy nondependent recreational users of prescription opioids: a randomized trial.

Background: Prescription opioids have substantial abuse potential. This study compared the positive subjective drug effects of a newly developed extended-release (ER) oxycodone (OC)/acetaminophen (acetyl-para-aminophenol [APAP]) formulation with those of immediate-release (IR) OC/APAP.

Methods: This randomized, double-blind, active- and placebo-controlled, 7-way crossover study enrolled healthy volunteers who were recreational prescription opioid users.

Complementary pharmacokinetic measures to further define the profile of once-daily OROS hydromorphone ER during single-dose and steady-state dosing.

Conventional measures such as maximum plasma concentration (C max ) and area under the concentration versus time curve (AUC) may be insufficient to fully describe the pharmacokinetic (PK) profile of extended-release (ER) formulations. A complementary measure, the half-value duration (HVD), corresponds to the period of time during a dosing cycle that plasma concentration is at or above half the value of the maximal concentration (i.e.

Biodistribution of diclofenac following repeated topical applications of two diclofenac sodium formulations to minipigs.

This study evaluated diclofenac concentrations in plasma, selected hind limb tissues and synovial fluid after repeated topical applications of two diclofenac formulations. Group 1 Gottingen minipigs (n = 18) were administered diclofenac sodium 2.0% topical solution twice daily on days 1-6 and once on day 7.

Oxidative biomarkers to assess the nanoparticle-induced oxidative stress.

Nanotechnology involves the creation and manipulation of materials at nanoscale levels to create products that exhibit novel properties. Engineered nanomaterials either metals (like carbon and silver) or metal oxides (like zinc oxide, magnesium oxide, and titanium oxide) induce toxicity and oxidative stress by generating free radicals. Various in vitro and in vivo models are available to estimate the oxidative stress induced by the nanoparticles.

Effect of dialkyl- [2-(1-oxa-3,4,9-triaza-fluoren-2-yl-methoxy)ethyl] amines on biogenic amines: new potential antidepressants.

A thorough survey of the literature has revealed that indole derivatives have shown various central nervous system activities. This study aims to evaluate the antidepressant activity of the newly synthesized dialkyl- [2-(1-oxa-3,4,9-triaza-fluoren-2-yl-methoxy)ethyl] amines and their effect on biogenic amines. In this study, the synthesized compounds were assessed by in-vivo antidepressant models, by forced swim test and tail suspension test in mice and effect of synthesized compounds on biogenic amines in brain in a chronic unpredictable stress model.

Novel mononuclear ruthenium(II) compounds in cancer therapy.

The present study was conducted to evaluate in vivo anticancer activity of two novel mononuclear ruthenium(II) compounds, namely Ru(1,10-phenanthroline)2(2-nitro phenyl thiosemicarbazone)Cl2 (Compound R1) and Ru (1,10-phenanthroline)2(2-hydroxy phenyl thiosemicarbazone)Cl2 (Compound R2) against Ehrlich ascites carcinoma (EAC) mice and in vitro cytotoxic activity against IEC-6 (small intestine) cell lines and Artemia salina nauplii using MTT [(3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide)] and BLT [brine shrimp lethality] assays respectively. The test ruthenium compounds at the doses 2 and 4 mg/kg body weight showed promising biological activity, especially in decreasing tumor volume, viable ascites cell counts and body weights. These compounds prolonged the life span (% ILS), mean survival time (MST) of mice bearing-EAC tumor.

Cardiovascular risk among university students from developed and developing nations.

Background: A key aspect in halting global increase in cardiovascular events is prevention and especially prevention at an early age. Unfortunately, global data regarding cardiovascular risk factors in the young are limited. Therefore the objectives of this study were to identify the most common cardiovascular risk factors among young adults in a university setting in both developed and developing countries.

Predictive models for drugs exhibiting negative food effects based on their biopharmaceutical characteristics.

Context: A drug is defined to exhibit food effects if its pharmacokinetic parameter, area under the curve (AUC₀₋∞) is different when co-administered with food in comparison with its administration on a fasted stomach. Food effects of drugs administered in immediate release dosage forms were classified as positive, negative, and no food effects.

Objective: In this study, predictive models for negative food effects of drugs that are stable in the gastrointestinal tract and do not complex with Ca²⁺ are reported.