314 research outputs found
Selecive Catalytic Reduction of NOx in Lean Burn Engine Exhaust by Highly Active Pt Supported on V-impregnated MCM-41
No full textOn the Pt/V/MCM-41 catalyst with 1wt% Pt and 4wt% V, the maximum conversion of NO reduction into N2+N2O by C3H6 was about 73%, which was 10% higher than on 1wt% Pt/silica, and this maximum conversion was maintained over a temperature range of 70.DEG.C. between 270 and 340.DEG.C.. (author abst.
Factors affecting the pharmacokinetics and pharmacodynamics of PEGylated liposomal irinotecan (IHL-305) in patients with advanced solid tumors
No full textHuali Wu,1 Jeffrey R Infante,2 Vicki L Keedy,3 Suzanne F Jones,2 Emily Chan,3 Johanna C Bendell,2 Wooin Lee,4 Whitney P Kirschbrown,1 Beth A Zamboni,5 Satoshi Ikeda,6 Hiroshi Kodaira,6 Mace L Rothenberg,3 Howard A Burris III,2 William C Zamboni1,7–9 1UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, 2Sarah Cannon Research Institute/Tennessee Oncology, PLLC, 3Vanderbilt University, Nashville, TN, 4Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 5Department of Mathematics, Carlow University, Pittsburgh, PA, USA; 6Yakult Honsha Co., Ltd., Medical Development Department, Tokyo, Japan; 7UNC Lineberger Comprehensive Cancer Center, 8UNC Institute for Pharmacogenomics and Individualized Therapy, 9Carolina Center for Cancer Nanotechology Excellence, University of North Carolina, Chapel Hill, NC, USA Abstract: IHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11). The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age and body composition (ratio of total body weight to ideal body weight [TBW/IBW]) were greater than the median age and TBW/IBW of the study had a 1.7-fold to 2.6-fold higher ratio of released CPT-11 area under the concentration versus time curve (AUC) to sum total CPT-11 AUC. Patients aged <60 years had a 1.3-fold higher ratio of percent decrease in monocytes at nadir to percent decrease in absolute neutrophil count at nadir as compared with patients aged ≥60 years. There was an inverse relationship between patient age and percent decrease in monocytes at nadir, ie, younger patients have a higher percent decrease in monocytes. Patients with a higher percent decrease in monocytes at nadir have a decreased plasma exposure of sum total CPT-11. The pharmacokinetics and pharmacodynamics of IHL-305 are consistent with those of other PEGylated liposomal carriers. Interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 was associated with age, body composition, and monocytes. Keywords: PEGylated liposome, irinotecan, CPT-11, IHL-305, pharmacokinetics, monocyte
A study of the reliability and validity of the Chinese version of the Dementia Rating Scale
No full textAuthor name used in this publication: Andrew M. H. Siu2004-2005 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishedVoR allowe
Population pharmacokinetics of PEGylated liposomal CPT-11 (IHL-305) in patients with advanced solid tumors
No full textTo investigate pharmacokinetics (PK) of encapsulated CPT-11, released CPT-11 and the active metabolite SN-38 following administration of IHL-305 and to identify factors that may influence IHL-305 PK. Plasma samples from 39 patients with solid tumors were collected in a phase I study. IHL-305 was administered as a 1 h IV infusion with doses ranging from 3.5 to 210 mg/m(2). Plasma concentrations of encapsulated CPT-11, released CPT-11 and SN-38 were used to develop a population PK model using NONMEMA (R). PK of encapsulated CPT-11 was described by 1-compartment model with nonlinear clearance and PK of released CPT-11 was described by a 1-compartment model with linear clearance for all patients. PK of the active metabolite SN-38 was described by a 2-compartment model with linear clearance for all patients. Covariate analysis revealed that gender was a significant covariate for volume of distribution of encapsulated CPT-11. V-encap in male patients is 1.5-fold higher compared with female patients. The developed population PK modeling approach is useful to predict PK exposures of encapsulated and released drug and can be applied to the more than 300 other nanoparticle formulations of anticancer agents that are currently in development. The effect of gender on PK of IHL-305 needs to be further evaluated.N
Phase I and pharmacokinetic study of IHL-305 (PEGylated liposomal irinotecan) in patients with advanced solid tumors
No full textPurpose IHL-305 is a novel PEGylated liposome containing irinotecan. This study examined the safety profile and pharmacokinetics of IHL-305 and established the maximum tolerated dose and recommended phase II dose (RP2D). Patients and methods In a standard 3 3 design, IHL- 305 was administered IV on day 1 of a 28-day treatment schedule. Subsequently, a 14-day treatment schedule was also explored. Two patient populations were evaluated separately: Patients with at least one wild-Type (wt) allele of UGT1A1 (UDP glucoronosyltransferase 1A1) wt/wt or wt/28 as one group (referred to as UGT1A1 wt group) and patients with UGT1A128 homozygous variant (28/28) as another group. Results Sixty patients were treated: 42 on the 28-day schedule and 18 on the 14-day schedule. Seven patients were homozygous variant (28/28). In the UGT1A1 wt group, the MTD and RP2D of IHL-305 was 160 mg/m2 every 28 days and 80 mg/m2 every 14 days. DLTs included nausea, vomiting, diarrhea, and neutropenia. The most common adverse events were nausea (75 %), vomiting (52 %), diarrhea (62 %), anorexia (57 %), and fatigue (57 %). At the MTD for both schedules, IHL-305 administration resulted in a high and prolonged exposure of sum total irinotecan, released irinotecan, and SN-38 in plasma. One partial response was observed in a patient with breast cancer and eight patients had stable disease for≥6 months. Conclusions IHL-305, a novel preparation of irinotecan encapsulated in liposomes, can be safely given to patients in a repeated fashion on a 4- or 2-week dosing schedule. © Springer-Verlag 2012.N
Factors Affecting the Pharmacokinetics and Pharmacodynamics of PEGylated Liposomal Irinotecan (IHL-305) in Patients with Advanced Solid Tumors
No full textIHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11). The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age and body composition (ratio of total body weight to ideal body weight [TBW/IBW]) were greater than the median age and TBW/IBW of the study had a 1.7-fold to 2.6-fold higher ratio of released CPT-11 area under the concentration versus time curve (AUC) to sum total CPT-11 AUC. Patients aged \u3c60 years had a 1.3-fold higher ratio of percent decrease in monocytes at nadir to percent decrease in absolute neutrophil count at nadir as compared with patients aged ≥60 years. There was an inverse relationship between patient age and percent decrease in monocytes at nadir, ie, younger patients have a higher percent decrease in monocytes. Patients with a higher percent decrease in monocytes at nadir have a decreased plasma exposure of sum total CPT-11. The pharmacokinetics and pharmacodynamics of IHL-305 are consistent with those of other PEGylated liposomal carriers. Interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 was associated with age, body composition, and monocytes
Applying IHL Targeting Rules to Practical Situations: Proportionality and Military Objectives
No full textThe IHL targeting rules are framed in relatively abstract terms and there is, unfortunately, no general agreement concerning precisely which objects constitute military objectives and concerning the relative values to be assigned to civilian losses and military advantages when computing the proportionality equation. The author encourages the development of a dialogue between all informed and interested parties, based in large part on case studies, to clarify the concepts.
Les règles du DIH sur le choix des objectifs sont rédigées en termes passablement abstraits et il n’y a malheureusement pas d’accord général au sujet de précisément quels objets constituent des objectifs militaires ainsi qu’au sujet des valeurs relatives à accorder aux pertes civiles et aux avantages militaires pour établir l’équation de proportionnalité. L’auteur préconise le développement d’un dialogue entre toutes les parties renseignées et intéressées, basé en grande partie sur des études de cas, dans le but de clarifier les concepts
It's just another war!
No full textThis article describes the increasing use of private military corporations (PMCs) and the implications for International Humanitarian Law (IHL). After considering the development of the laws of war alongside the rise of corporations the author questions the likely effect this new development may have for sovereign states and the notion that only states have the right to control military power. The author argues that this development will have consequences for sovereign democracies, IHL and Human Rights
Responding the Internationalisation of Conflict: Rule of Law based Humanitarian Law Approachesas Pioneers of Legal Globalisation
No full textWhat interpretative role can the historical development of International Humanitarian Law (IHL) norms play in the current discussion on the globalization of law in general? To answer this question, the article firstly highlights from a theoretical perspective the fragmentary effects of the phenomena of globalization on law in general to set the discursive playing field. Based on these findings, the author shows potential normative and institutional answers provided by IHL on the truly global phenomenon of armed conflicts. To demonstrate the ongoing development and normative reinterpretations of IHL norms in the interdependent system of customary rules and treaty-based rules, the article draws a line of reception from the norms of the St. Petersburg Declaration (1868) to the influential Customary International Law Study of the International Committee of the Red Cross (2005) and recent IHL conventions such as the convention on cluster munitions (2008). Thereby, a special emphasis is given to the broad global acceptance of the relevant IHL norms despite its rather weak enforcement mechanisms.What interpretative role can the historical development of International Humanitarian Law (IHL) norms play in the current discussion on the globalization of law in general? To answer this question, the article firstly highlights from a theoretical perspective the fragmentary effects of the phenomena of globalization on law in general to set the discursive playing field. Based on these findings, the author shows potential normative and institutional answers provided by IHL on the truly global phenomenon of armed conflicts. To demonstrate the ongoing development and normative reinterpretations of IHL norms in the interdependent system of customary rules and treaty-based rules, the article draws a line of reception from the norms of the St. Petersburg Declaration (1868) to the influential Customary International Law Study of the International Committee of the Red Cross (2005) and recent IHL conventions such as the convention on cluster munitions (2008). Thereby, a special emphasis is given to the broad global acceptance of the relevant IHL norms despite its rather weak enforcement mechanisms
Introducing a sliding-scale of obligations to address the fundamental inequality between armed groups and states?
No full textIn a debate with Prof. Yuval Shany, the author argues that the equality of belligerents in international humanitarian law of non-international armed conflicts should be abandoned, because it either subjects many armed groups to unrealistic requirements they cannot comply with or it limits the obligations of governmental forces to minimal obligations. The author provides examples of fields in which IHL of non-international armed conflicts, which becomes increasingly similar to IHL of international armed conflicts, is unrealistic for most armed groups. The author suggest rather a sliding-scale of obligations for armed groups, that will increase according to the intensity of violence and the degree of organization of the group
- …
