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Cherry Valley, IL, United States

Natale J.J.,5150 Center Avenue | Spinelli T.,Helsinn Healthcare SA | Calcagnile S.,Helsinn Healthcare SA | Lanzarotti C.,Helsinn Healthcare SA | And 3 more authors.
Journal of Oncology Pharmacy Practice | Year: 2015

Neurokinin-1 (NK1) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT3) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU) - a new NK1 RA - and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug-drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates. © The Author(s) 2015. Source

Mordin M.,Market Access and Outcomes Strategy | Masaquel C.,Market Access and Outcomes Strategy | Abbott C.,Ipsen Inc. | Copley-Merriman C.,Market Access and Outcomes Strategy
BMJ open | Year: 2014

OBJECTIVE: To describe the health-related quality of life (HRQOL) burden of cervical dystonia (CD) and report on the HRQOL and patient perception of treatment benefits of abobotulinumtoxinA (Dysport).DESIGN: The safety and efficacy of a single injection of abobotulinumtoxinA for CD treatment were evaluated in a previously reported international, multicenter, double-blind, randomised trial. HRQOL measures were assessed in the trial and have not been previously reported.SETTING: Movement disorder clinics in the USA and Russia.PARTICIPANTS: Patients had to have a diagnosis of CD with symptoms for at least 18 months, as well as a total Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) score of at least 30; a Severity domain score of at least 15; and a Disability domain score of at least 3. Key exclusion criteria included treatment with botulinum toxin type A (BoNT-A) or botulinum toxin type B (BoNT-B) within 16 weeks of enrolment.INTERVENTIONS: Patients were randomised to receive either 500 U abobotulinumtoxinA (n=55) or placebo (n=61).PRIMARY AND SECONDARY OUTCOME MEASURES: Efficacy assessments included TWSTRS total (primary end point) and subscale scores at weeks 0, 4, 8, 12; a pain visual analogue scale at weeks 0 and 4; and HRQOL assessed by the SF-36 Health Survey (SF-36; secondary end point) at weeks 0 and 8.RESULTS: Patients with CD reported significantly greater impairment for all SF-36 domains relative to US norms. Patients treated with abobotulinumtoxinA reported significantly greater improvements in Physical Functioning, Role Physical, Bodily Pain, General Health and Role Emotional domains than placebo patients (p≤0.03 for all). The TWSTRS was significantly correlated with Physical Functioning, Role Physical and Bodily Pain scores, for those on active treatment.CONCLUSIONS: CD has a marked impact on HRQOL. Treatment with a single abobotulinumtoxinA injection results in significant improvement in patients' HRQOL.TRIAL REGISTRATION NUMBER: The trial is registered at ClinicalTrials.gov, numbers NCT00257660 and NCT00288509. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. Source

Ipsen, Ipsen Inc. and Alco Standard Corporation | Date: 1985-10-01


Wu J.,University of Pennsylvania | Ruiz-Rodriguez J.,ETH Zurich | Comstock J.M.,Ipsen Inc. | Dong J.Z.,Ipsen Inc. | Bode J.W.,ETH Zurich
Chemical Science | Year: 2011

The synthesis of the bioactive form of human glucagon-like peptide, GLP-1 (7-36), by the chemoselective ligation of two unprotected fragments, a C-terminal peptide α-ketoacid with an N-terminal peptide hydroxylamine, is reported. No reagents are required for the ligation and no byproducts are produced. Unprotected glutamic acid, histidine, arginine, lysine, serine, and tyrosine residues do not interfere with the ligation; no side products arising from undesired reactions of the side chains are detected. This synthesis is the first reported example of the application of the α-ketoacid-hydroxylamine amide ligation to the synthesis of a complex, unprotected peptide. Its success underscores the potential broad utility of this amide ligation for the synthesis of complex peptides and related targets. © The Royal Society of Chemistry 2011. Source

The article examines why defining gas quenching in bar pressure no longer applies, why a new definition is needed, and how this definition enables a better understanding of which steel and what cross section can be hardened via gas quenching. The result is a totally nonuniform heat transfer rate on various surfaces of different parts, which depends on a number of variables and factors. This uneven transitory step creates huge temperature differentials, and is the major factor in distortion when quenching in these media. Gas quenching is a pure, convective type single-phase quench. Gas species, pressure, and velocity are the main controlling factors. A procedure developed by Ipsen to predict the hardness and structure after gas quenching makes use of the necessary cooling rate in the temperature region of the pearlite and ferrite formation. Source

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