A Continuous Intestinal Absorption Model to Predict Drug Enterohepatic Recirculation in Healthy Humans: Nalbuphine as a Model Substrate.

Nalbuphine (NAL) is a κ-agonist/μ-antagonist opioid being developed as an oral extended formulation (ER) for the treatment of chronic cough in idiopathic pulmonary fibrosis and itch in prurigo nodularis. NAL is extensively glucuronidated and likely undergoes enterohepatic recirculation (EHR). The purpose of this work is to develop pharmacokinetic models for NAL absorption and enterohepatic recirculation (EHR).

A population pharmacokinetic-pharmacodynamic model evaluating efficacy of nalbuphine extended-release in patients with prurigo nodularis.

Aims: Population pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) models were used to describe the exposure-response (E-R) relationship between nalbuphine exposure and two widely used rating scales for itch: the Numerical Rating Scale for the subject's 'average'; itch experience (NRS-AV) and the Worst Itch (WI-NRS), with 24-h recall. Simulations based on the model E-R relationship were used to support dose selection for Phase 3 clinical trials and were evaluated with a target of reducing the 7-day average of the 24-h WI-NRS by at least 30% from baseline in most of the analysis population.

Methods: Data from two clinical trials (NCT02373215: 9 healthy subjects; NCT02174419: 62 subjects with PN), in patients with prurigo nodularis (PN) with moderate to severe itch who received treatment with either of two doses of nalbuphine extended release (ER) or placebo, were used for the analysis.

The lasso-loop, lasso-mattress and simple-cinch stitch for arthroscopic rotator cuff repair: are there biomechanical differences?

Purpose: Various stitching techniques have been described to facilitate arthroscopic repair of rotator cuff tears. The aim of the present study was to compare the biomechanical properties of the lasso-loop, lasso-mattress and simple-cinch stitch for rotator cuff repair.

Methods: Twelve infraspinatus tendons were harvested from sheep and split in half.

Biomechanical evaluation of the simple cinch stitch for arthroscopic rotator cuff repair.

Background: The tissue-suture interface is described as the most vulnerable and susceptible area in the muscle-tendon-bone construction of arthroscopic rotator cuff repair. Various stitching techniques have been described to enhance the strength, fixation and stability of the repair, but technical and biomechanical challenges remain. Purpose was to examine the biomechanical properties of the simple cinch stitch in comparison to other stitches commonly used for rotator cuff repair.

The Simple Cow Hitch Stitch Technique for Arthroscopic Rotator Cuff Repair and Stabilization Using Knotless Suture Anchors.

The tissue-suture interface is the most vulnerable and challenging part of adequate restoration and fixation in rotator cuff repair. We describe a simple stitch technique for arthroscopic rotator cuff repair using knotless suture anchors based on the cow hitch. The simple cow hitch stitch technique is easy to perform, especially under difficult conditions, and provides excellent initial fixation strength as required for integration of the reinserted cuff and for shoulder stabilization.

Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus.

Background: Uremic pruritus is a common and deleterious condition among hemodialysis (HD) patients. Central gating of μ/κ opiate circuitry plays an important role in mediating and countering pruritogenic sensation. The objective of this study was to assess the safety and pharmacokinetics (PK) of the mixed μ-antagonist/κ-agonist nalbuphine, administered orally as nalbuphine HCl extended release (ER) tablets in HD patients, and explore its effect on pruritus.

A0001 in Friedreich ataxia: biochemical characterization and effects in a clinical trial.

This study tested the ability of A0001 (α-tocopheryl quinone; EPI-A0001), a potent antioxidant, to improve in vitro measures, glucose metabolism, and neurological function in Friedreich ataxia. We used an in vitro study of protection from cell toxicity followed by a double-blind, randomized, placebo-controlled trial of 2 doses of A0001 in 31 adults with Friedreich ataxia. The primary clinical trial outcome was the Disposition Index, a measure of diabetic tendency, from a frequently sampled intravenous glucose tolerance test, evaluated 4 weeks into therapy.

Use of an adaptive study design in single ascending-dose pharmacokinetics of A0001 (α-tocopherylquinone) in healthy male subjects.

A0001 (α-tocopherylquinone) is a potent antioxidant currently in development for the treatment of symptoms associated with inherited mitochondrial disorders. A0001 pharmacokinetics were studied in a single-blind, adaptive design study following a single daily oral dose of placebo (n = 2) or ascending doses of A0001 (n = 8) at 0.25 and 0.

Antimicrobial resistance and pathogenicity of Escherichia coli isolated from common dairy products in the Lebanon.

In a recent study, bacteria have been isolated from popular Lebanese dairy products, which had been collected in the Beqaa Valley, in north-eastern Lebanon. The foods investigated were two cheeses (shankleesh and baladi) and a dried fermented mixture of yogurt and wheat grains (kishk). Bacterial colonies on McConkey and sorbitol-McConkey agar that showed the morphology of Escherichia coli were biochemically tested and then classified, using PCR-based assays, into the various strains of pathogenic and non-pathogenic E.

The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.

Purpose: The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs.

Methods: The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate.

Single dose pharmacokinetics and bioavailability of nevirapine in healthy volunteers.

The results of two randomized, single-dose, crossover bioavailability studies are presented which describe the pharmacokinetics and oral bioavailability of nevirapine, a novel nonnucleoside antiretroviral drug. In the first study 12 healthy male volunteers received nevirapine 15 mg via short-term i.v.

Solubilization and in vitro spermicidal assessment of nonoxynol-9 and selected fractions using rabbit spermatozoa.

Selected oligomers representing the high, medium, and low molecular weight fractions of the spermicidal agent Nonoxynol-9 (N-9) were separated by HPLC. Nonoxynol-9 and the isolated fractions were formulated with polyvinylpyrrolidone (PVP) in order to increase their water solubility, particularly that of the insoluble low molecular weight fraction. The in vitro spermicidal activity of three molecular weight fractions were compared to that of N-9, using rabbit spermatozoa, at equimolar concentrations.

Development of an HPLC assay for the analysis of tetrafluoroputrescine--a putrescine analog.

A simple reverse-phase liquid chromatographic system with ultraviolet detection at 254 nm for tetrafluoroputrescine (TFP), a putrescine analog, is described. The assay involves precolumn derivatization of TFP with dansyl chloride at pH 6.8-7.

Detection of tetrafluoroputrescine in RBCs by fluorine-19 nuclear magnetic resonance spectroscopy.

Fluorine-19 nuclear magnetic resonance spectroscopy is used to detect the in vitro uptake of tetrafluoroputrescine, a novel putrescine analogue, in red blood cells.