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Subbarayan S.,Cleveland Clinic | Kipnes M.,Cetero Research
Expert Opinion on Pharmacotherapy | Year: 2011

Introduction: The ever-increasing burden of type 2 diabetes mellitus (T2DM) and inadequate control in the majority of patients has led to a quest for newer therapeutic options. There have been recent exciting advances in the treatment of T2DM, targeting the enteroinsular axis with incretin-based therapies that include the dipeptidyl peptidase IV (DPP-IV) inhibitors. Areas covered: The background, pharmacodynamic and pharmacokinetic profile of sitagliptin and important clinical trials with this drug are discussed in this paper. This review is intended to provide a comprehensive overview of the DPP-IV inhibitor sitagliptin, its clinical use and an expert opinion about its place in the treatment algorithm of diabetes management. Expert opinion: Sitagliptin is a well-tolerated, moderately efficacious, weight-neutral oral antidiabetic agent, with a low incidence of hypoglycemia. It may have a particular role in the management of diabetic patients with kidney or liver dysfunction. Animal studies indicate a protective effect on the pancreatic beta cell, thus limiting the progression of the disease, but this remains to be proven in humans. © Informa UK, Ltd. Source

Lehman P.A.,Cetero Research
International journal of pharmaceutical compounding | Year: 2012

An in vitro human percutaneous absorption study was conducted to assess the delivery of ketoprofen and testosterone from two base formulations, a Pluronic lecithin organogel and Pentravan Cream. Each formulation was applied to ex vivo human trunk skin (from three skin donors) on triplicate sections mounted onto Franz Diffusion Cells. Following a 5-mcL/cm2 applied dose, serial dermal receptor solutions were collected over 48 hours. For both compounds, a greater rate and extent of absorption was found from the Pentravan formulation than from the Pluronic lecithin organogel formulation: 3.8-fold greater for ketoprofen, 1.7-fold greater for testosterone, for amount absorbed. Source

Sloan-Lancaster J.,Eli Lilly and Company | Abu-Raddad E.,Eli Lilly and Company | Polzer J.,Eli Lilly and Company | Miller J.W.,Eli Lilly and Company | And 4 more authors.
Diabetes Care | Year: 2013

OBJECTIVE-Inflammation is associated with pancreatic β-cell apoptosis and reduced insulin sensitivity. Literature suggests that interleukin (IL)-1β may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). This study aimed to determine the efficacy, safety, and tolerability of LY2189102, a neutralizing IL-1b antibody, in T2DM patients. RESEARCH DESIGN AND METHODS-Phase II, randomized, double-blind, parallel, placebo-controlled study of subcutaneous LY2189102 (0.6, 18, and 180 mg) administered weekly for 12 weeks in T2DM patients on diet and exercise, with or without approved antidiabetic medications. RESULTS-LY2189102 reduced HbA1c at 12 weeks (adjusted mean differences versus placebo: 20.27, 20.38 and 20.25% for 0.6, 18 and 180 mg doses, respectively), and fasting glucose at multiple time points compared with placebo. LY2189102 also reduced postprandial glycemia, and inflammatory biomarkers, including hs-CRP and IL-6. LY2189102 was generally well tolerated. CONCLUSIONS-Weekly subcutaneous LY2189102 for 12 weeks was well tolerated, modestly reduced HbA1c and fasting glucose, and demonstrated significant anti-inflammatory effects in T2DM patients. Neutralizing IL-1β holds promise as a convenient adjuvant treatment for T2DM. © 2013 by the American Diabetes Association. Source

Barchuk W.T.,Janssen Research and Development | Salapatek A.M.,McMaster University | Ge T.,Janssen Research and Development | D'Angelo P.,Cetero Research | Liu X.,Janssen Research and Development
Journal of Allergy and Clinical Immunology | Year: 2013

Background: H1-receptor inverse agonists are used effectively for treating several symptoms of allergic rhinitis, including nasal itching, rhinorrhea, and sneezing, although most agents are not very effective in treating nasal congestion. Objective: This study evaluated the relative efficacy of a novel selective H3-receptor antagonist, JNJ-39220675, in preventing nasal congestion induced by exposing participants with ragweed allergy to ragweed allergen in an environmental exposure chamber model. Methods: In this single-dose, patient-blind, double-dummy, placebo- and active-controlled, phase IIa cross-over study, 53 participants were randomized to JNJ-39220675 plus placebo, placebo plus pseudoephedrine, or only placebo. The primary efficacy assessment was change in nasal patency assessed by measuring the minimal cross-sectional area of the nasal cavity by using acoustic rhinometry. Secondary assessment included total nasal symptom scores (TNSSs) over the 8-hour environmental exposure chamber exposure period. Results: Smaller decreases in minimal cross-sectional area were observed after JNJ-39220675 (least square mean difference, -0.126; P =.06) and pseudoephedrine (least square mean difference, -0.195; P =.004) treatment compared with placebo. The means for the baseline-adjusted area under the curve of TNSSs were significantly smaller for JNJ-39220675 (P =.0003) and pseudoephedrine (P =.04) versus placebo. JNJ-39220675 was significantly effective in treating all 4 individual symptoms (P ≤.05 for all scores) compared with placebo, whereas pseudoephedrine only showed a trend for improvement in individual symptom scores of the TNSS. Insomnia was the most frequent adverse event (17.3%) associated with JNJ-39220675 treatment. Conclusion: Prophylactic treatment with the H 3-antagonist JNJ-39220675 relieved allergen-induced nasal congestion by using standard nasal symptom scoring; however, in contrast to pseudoephedrine, it only showed a trend for increasing nasal patency by using objective measures. © 2013 American Academy of Allergy, Asthma and Immunology. Source

Lehman P.A.,PRACS Institute | Franz T.J.,PRACS Institute | Franz T.J.,Cetero Research
Skin Pharmacology and Physiology | Year: 2012

Purpose: To develop a simple pharmacodynamic (PD) assay for the evaluation of the bioequivalence of topically applied retinoid products. Methods: Daily applications of products containing tretinoin or adapalene were made to the forearms of human subjects for up to 21 days. Percutaneous absorption was enhanced through the use of polyethylene film occlusion (5 h). Pharmacologic activity was assessed through the daily measurement of three cutaneous responses intimately linked to retinoid-induced changes in epidermal differentiation: (1) erythema; (2) exfoliation (scaling/peeling), and (3) increased transepidermal water loss. Results: The PD model exhibited the sensitivity and specificity required to function as a bioequivalence surrogate. It was possible to differentiate between: (1) three concentrations of tretinoin in a commercial cream product line; (2) two concentrations of tretinoin in a commercial gel product line; (3) different vehicles (gel vs. cream) containing the same concentration of tretinoin, and (4) tretinoin and adapalene at the same concentration. The applicability of this model for bioequivalence testing was established by showing that it had sufficient power to determine that three test tretinoin cream products and two approved generic tretinoin gel products were equivalent to their corresponding reference products. Conclusions: A surrogate PD model to assess retinoid bioequivalence has been developed. Copyright © 2012 S. Karger AG, Basel. Source

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