Deirdre D'Arcy - Academia.edu (original) (raw)

Papers by Deirdre D'Arcy

European Journal of Pharmaceutics and Biopharmaceutics

reproduction in any medium, provided you give appropriate credit to the original author(s) and th... more reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. carbon dioxide 30 [27-35] mmHg and median temperature 37.1 [36.8-37.3]°C. After removal of artefacts, the mean monitoring time was 22 h08 (8 h54). All patients had impaired cerebral autoregulation during their monitoring time. The mean IAR index was 17 (9.5) %. During H 0 H 6 and H 18 H 24 , the majority of our patients; respectively 53 and 71 % had an IAR index > 10 %. Conclusion According to our data, patients with septic shock had impaired cerebral autoregulation within the first 24 hours of their admission in the ICU. In our patients, we described a variability of distribution of impaired autoregulation according to time. References Schramm P, Klein KU, Falkenberg L, et al. Impaired cerebrovascular autoregulation in patients with severe sepsis and sepsis-associated delirium. Crit Care 2012; 16: R181. Aries MJH, Czosnyka M, Budohoski KP, et al. Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury. Crit. Care Med. 2012.

Heat and Mass Transfer, Oct 2, 2017

This paper applies boundary layer theory to the process of drug dissolution in the USP (United St... more This paper applies boundary layer theory to the process of drug dissolution in the USP (United States Pharmacopeia) Flow Through Apparatus. The mass transfer rate from the vertical planar surface of a compact within the device is examined. The theoretical results obtained are then compared with those of experiment. The paper also examines the effect on the dissolution process caused by the interaction between natural and forced convection within the apparatus and the introduction of additional boundaries.

Dissolution Technologies, 2022

Performance testing of parenteral products represents a broad arena of product types, test equipm... more Performance testing of parenteral products represents a broad arena of product types, test equipment, and analytical challenges. This Stimuli article is one in a series of Stimuli articles on product performance testing focused on common methodological approaches used and challenges encountered in the field of performance testing of injectable products. The article is complementary to In Vitro Release Test Methods for Parenteral Drug Preparations <1001> and takes into account the contents and acknowledges current trends in test apparatus and conditions, medium selection, and separation techniques. Limitations of current practices are presented, and recommendations highlight the need for biorelevant and predictive test environments, test standardization, and an understanding of the impact of the test conditions on the release kinetics and interpretation of test results.

Journal of Antimicrobial Chemotherapy, Dec 18, 2017

Objectives: To develop a pharmacokinetic model describing total and unbound teicoplanin concentra... more Objectives: To develop a pharmacokinetic model describing total and unbound teicoplanin concentrations in patients with haematological malignancy and to perform Monte Carlo simulations to evaluate target attainment of unbound trough concentrations with various dose regimens. Methods: This was a hospital-based clinical trial (EudraCT 2013-004535-72). The dosing regimen was 600/800 mg q12h for three doses then 600/800 mg daily. Serial total and unbound teicoplanin concentrations were collected. Maximum protein binding was estimated from serum albumin concentration. Population pharmacokinetic analyses and Monte Carlo simulations were conducted using Pmetrics V R. Target total and unbound trough concentrations were !20 and !1.5 mg/L, respectively. Results: Thirty adult patients were recruited with a mean (SD) bodyweight of 69.1 (15.8) kg, a mean (SD) CL CR of 72 (41) mL/min and a median (IQR) serum albumin concentration of 29 (4) g/L. A three-compartment complex binding pharmacokinetic model best described the concentration-time data. Total and unbound teicoplanin concentrations were related by serum albumin concentration and a dissociation constant. CL CR and bodyweight were supported as covariates for CL and volume of the central compartment, respectively. Dosing simulations showed that high CL CR was associated with reduced probability of achieving target total and unbound trough concentrations. Low serum albumin concentration was associated with a reduced probability of attaining target total but not unbound trough concentrations. A method to estimate the unbound teicoplanin concentration from the measured total concentration at different serum albumin concentration was demonstrated. Conclusions: Standard teicoplanin dosing regimens should be used with caution in patients with haematological malignancy. Bodyweight, CL CR and serum albumin concentration are important considerations for appropriate dosing.

Clinical Microbiology and Infection, Sep 1, 2017

Objectives: To describe the population pharmacokinetics of teicoplanin in adult patients with hae... more Objectives: To describe the population pharmacokinetics of teicoplanin in adult patients with haematological malignancies receiving higher than standard doses, and to perform Monte Carlo simulations to determine dosing regimens associated with optimal teicoplanin concentrations. Methods: This was a hospital-based clinical trial (EudraCT 2013e004535e72). Nine blood samples were collected on Day 3, plus single trough samples on Days 7 and 10, and 24 and 48 hours after the last dose. Teicoplanin minimum inhibitory concentrations were determined for Gram-positive isolates from study patients. Population pharmacokinetic analyses and Monte Carlo dosing simulations were undertaken using Pmetrics. Results: Thirty adult haematological malignancy patients were recruited with a mean (SD) loading dose, age, total body weight, and creatinine clearance of 9.5 (1.9) mg/kg, 63 (12) years, 69.1 (15.8) kg, and 72 (41) mL/min, respectively. A three-compartment linear pharmacokinetic model best described the teicoplanin concentration data. Covariates supported for inclusion in the final model were creatinine clearance for clearance and total body weight for volume of the central compartment. The median (IQR) area under the concentration-time curve from 48 to 72 hours (AUC 48e72h) was 679 (319) mg.h/L. There was a strong correlation between the AUC 48e72h and trough concentration at 72 hours (Pearson correlation coefficient 0.957, p <0.001). Dosing simulations showed that administration of five loading doses at 12-hourly intervals, stratified by total body weight and creatinine clearance, increased the probability of achieving target concentrations within 72 hours. Conclusions: To increase the number of patients achieving optimal teicoplanin concentrations an individualized dosing approach, based on body weight and creatinine clearance, is recommended.

Electronic journal of general medicine, May 1, 2023

2022 APS Special Issue

Dissolution testing is widely used during all stages of drug development. The potential to develo... more Dissolution testing is widely used during all stages of drug development. The potential to develop an imaging analysis method to automatically detect agglomerations during dissolution testing has recently been explored. The stages of the method development were manual observation of pre-recorded videos from the dissolution testing, choice of parameters for agglomerate identification and 2-stage method validation (internal and external). This work presents the two main challenges faced during the agglomeration identification method (AIM) development a) attaining an optimal number of particle detections in a video frame and b) discerning different objects (e.g., air bubbles, single particles and agglomerates) based on their specifications.

SA-PO636 Exploring population Pharmacokinetics of Vancomycin While Using Different Anticoagulant ... more SA-PO636 Exploring population Pharmacokinetics of Vancomycin While Using Different Anticoagulant Modalities during Continuous Venovenous Haemodiafiltration (CVVHDF) Session Information  Pharmacokinetics, Pharmacodynamics, Pharmacogenomics November 04, 2017 | Location: Hall H Abstract Time: 10:00 AM 10:00 AM Category: Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics  1601 Pharmacokinetics, Pharmacodynamics, Pharmacogenomics Authors  O'Keeffe, Hannah Marie, Tallaght Hospital, Dublin, Ireland  Munshi, Reema Mohammad, Trinity College Dublin, Dublin, Ireland  Coyle, Mary, Tallaght Hospital, Dublin, Ireland  Deasy, Evelyn, Tallaght Hospital, Dublin, Ireland  Donnelly, Maria B, Tallaght Hospital, Dublin, Ireland  Fitzpatrick, Gerard J, Tallaght Hospital, Dublin, Ireland  Lavin, Peter J., Tallaght Hospital, Dublin, Ireland  D'Arcy, Deirdre M, Trinity College Dublin, Dublin, Ireland

European Journal of Pharmaceutics and Biopharmaceutics, 2020

In vitro-in vivo relations for the parenteral liposomal formulation of Amphotericin B.

C45. DIAGNOSTIC TECHNIQUES AND MONITORING: FROM BENCH TO BEDSIDE, 2010

Page 1. / Thematic Poster Session / Tuesday, May C45 DIAGNOSTIC TECHNIQUES AND MONITORING: FROM B... more Page 1. / Thematic Poster Session / Tuesday, May C45 DIAGNOSTIC TECHNIQUES AND MONITORING: FROM BENCH TO BEDSIDE 18/8:15 AM-4:00 PM / Area H, Hall G (First Level), Morial Convention Center A Description ...

Intensive care medicine experimental, 2016

Introduction: Critically ill children in the pediatric intensive care unit (PICU) are at high ris... more Introduction: Critically ill children in the pediatric intensive care unit (PICU) are at high risk for developing nutritional deficiencies and undernutrition is known to be a risk factor for morbidity and mortality. Malnutrition represents a continuous spectrum ranging from marginal nutrient status to severe metabolic and functional alterations and this in turn, affects clinical outcome. Objectives: The aim of the study was to assess nutritional status of critically ill children admitted to the PICU and its association to clinical outcomes. Methods: Critically ill children age 6 months to 18 years were prospectively enrolled on PICU admission. Nutritional status was assessed by weight for age (WFA: underweight), weight for height (WFH: wasting), height for age (HFA: stunting) z-scores and mid upper arm circumference (MUAC: wasting) according to the WHO. (1,2) Malnutrition was defined as mild, moderate, and severe if z-scores were > −1, > − 2, and > −3, respectively. Hospital and PICU length of stay (LOS), duration of mechanical ventilation (MV), and risk of mortality (ROM) by the Pediatric Index of Mortality 2 (PIM2) were obtained. Sensitivity and specificity of the MUAC to identify children with wasting (WFH) were calculated. Results: Two hundred and fifty children (136 males), aged 81 months (23-167; median (25-75 th IQR)), were prospectively included in the study. The hospital LOS was 8 (4-16) days; PICU LOS: 2 (1-4) days; duration of MV, 0 (0-1.5) days;

Journal of Pharmacy and Pharmacology, 2005

The aim of this work was to investigate the dissolution rate from both the curved and planar surf... more The aim of this work was to investigate the dissolution rate from both the curved and planar surfaces of cylindrical compacts of benzoic acid, which were placed centrally and non-centrally at the base of the vessel of the paddle dissolution apparatus. The effect of fixing the compacts to a particular position on the variability of dissolution results was also examined. In addition, computational fluid dynamics (CFD) was used to simulate fluid flow around compacts in the different positions in the vessel, and the relationship between the local hydrodynamics in the region of the compacts and the dissolution rate determined. The dissolution rate was found to increase from the centre position to the off-centre positions for each surface examined. There was a corresponding increase in maximum fluid velocities calculated from the CFD fluid flow simulations at a fixed distance from the compact. There was less variability in dissolution from compacts fixed to any of the positions compared w...