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Trough focus curve

Fawzy Elbarbry
After more than six decades of its use as the mainstay antibiotic for the treatment of multidrug-resistant Gram-positive bacterial infections, dosing and monitoring of vancomycin therapy have not been optimized. The current vancomycin therapeutic guidelines recommend empiric doses of 15-20 mg/kg administered by intermittent infusion every 8-12 h in patients with normal kidney function. Additionally, the guidelines recommend trough concentration of 15-20 mg/L as a therapeutic goal for adult patients with severe infections...
December 19, 2017: European Journal of Drug Metabolism and Pharmacokinetics
Kris S Chaisanguanthum, Helen H Shen, Philip N Sabes
Dorsal premotor (PMd) and primary motor (M1) cortices play a central role in mapping sensation to movement. Many studies of these areas have focused on correlation-based tuning curves relating neural activity to task or movement parameters, but the link between tuning and movement generation is unclear. We recorded motor preparatory activity from populations of neurons in PMd/M1 as macaque monkeys performed a visually guided reaching task and show that tuning curves for sensory inputs (reach target direction) and motor outputs (initial movement direction) are not typically aligned...
March 22, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Antonio D'Avolio, Debora Pensi, Lorena Baietto, Giovanni Pacini, Giovanni Di Perri, Francesco Giuseppe De Rosa
Infections, including sepsis, are associated with high mortality rates in critically ill patients in the intensive care unit (ICU). Appropriate antibiotic selection and adequate dosing are important for improving patient outcomes. Daptomycin is bactericidal in bloodstream infections caused by Staphylococcus aureus and other Gram-positive pathogens cultured in ICU patients. The drug has concentration-dependent activity, and the area under the curve/minimum inhibitory concentration ratio is the pharmacokinetic/pharmacodynamic (PK/PD) index that best correlates with daptomycin activity, whereas toxicity correlates well with daptomycin plasma trough concentrations (or minimum concentration [C min])...
August 2016: Drugs
John P Prybylski
STUDY OBJECTIVE: To determine the strength of evidence for better clinical outcomes in patients with Staphylococcus aureus bacteremia who had vancomycin trough levels of 15-20 mg/L. DESIGN: Meta-analysis of 14 observational cohort studies. PATIENTS: A total of 1677 patients, representing geriatric and unspecified inpatients, who received standard dosing of vancomycin for the treatment of S. aureus bacteremia and who had trough level goals of 15-20 mg/L...
October 2015: Pharmacotherapy
M A Sikma, E M van Maarseveen, E A van de Graaf, J H Kirkels, M C Verhaar, D W Donker, J Kesecioglu, J Meulenbelt
Annually, about 8000 heart and lung transplantations are successfully performed worldwide. However, morbidity and mortality still pose a major concern. Renal failure in heart and lung transplant recipients is an essential adverse cause of morbidity and mortality, often originating in the early postoperative phase. At this time of clinical instability, the kidneys are exposed to numerous nephrotoxic stimuli. Among these, tacrolimus toxicity plays an important role, and its pharmacokinetics may be significantly altered in this critical phase by fluctuating drug absorption, changed protein metabolism, anemia and (multi-) organ failure...
September 2015: American Journal of Transplantation
Hiroyuki Kobayashi, Kazuhiro Sato, Takenori Niioka, Hajime Miura, Hiroshi Ito, Masatomo Miura
INTRODUCTION: The present study investigated the effects of patients' genetic variations in the pharmacokinetics of gefitinib at steady-state. We analyzed 31 Japanese patients with non-small-cell lung cancer (NSCLC) who had been treated with gefitinib. We focused on common polymorphisms within important gefitinib exposure genes, including cytochromes P450 (CYPs) CYP3A4*1G, CYP3A5 (*3), and CYP2D6 (*5 and *10) and ATP-binding cassette (ABC) ABCG2 (421C>A) and ABCB1 (1236C>T, 2677G>T/A, and 3435C>T)...
July 2015: Clinical Lung Cancer
Fuad Shihab, Uwe Christians, Lonnie Smith, Jason R Wellen, Bruce Kaplan
Mammalian target of rapamycin (mTOR)-inhibitor-containing immunosuppressive regimens have been developed as part of calcineurin inhibitor (CNI) minimization/withdrawal strategies for renal transplant recipients, with the goal of avoiding CNI-associated nephrotoxicity. This review focuses on the pharmacokinetic interactions and exposure-response relationships of mTOR inhibitors and tacrolimus (TAC), the most widely used CNI. We also discuss key randomized clinical studies that have evaluated use of this combination in renal transplantation...
June 2014: Transplant Immunology
Olga Krivosheeva, Andra Dėdinaitė, Markus B Linder, Robert D Tilton, Per M Claesson
Hydrophobins are relatively small globular proteins produced by filamentous fungi. They display unusual high surface activity and are implied as mediators of attachment to surfaces, which has resulted in high scientific and technological interest. In this work we focus on kinetic and equilibrium aspects of adsorption and desorption properties of two representatives of class II hydrophobins, namely HFBI and HFBII, at a negatively charged hydrophilic solid/water interface and at the air/water interface. The layers formed at the air/liquid interface were examined in a Langmuir trough, whereas layers formed at the solid/liquid interface were studied using dual polarization interferometry (DPI) under different flow conditions...
February 26, 2013: Langmuir: the ACS Journal of Surfaces and Colloids
David I Sandberg, M Melissa Peet, Mark D Johnson, Phaedra Cole, Tulay Koru-Sengul, Ali W Luqman
OBJECT: The authors hypothesized that chemotherapy infusions directly into the fourth ventricle might potentially play a role in treating malignant fourth ventricular tumors. The study tested the safety and pharmacokinetics of short- and long-term infusions of methotrexate into the fourth ventricle in a new nonhuman primate model. METHODS: Six rhesus monkeys underwent posterior fossa craniectomy and catheter insertion into the fourth ventricle. In Group I (3 animals), catheters were externalized, and lumbar drain catheters were placed simultaneously to assess CSF distribution after short-term methotrexate infusions...
May 2012: Journal of Neurosurgery. Pediatrics
Timothy F Duda, Ying-Tsong Lin, D Benjamin Reeder
A study of 400 Hz sound focusing and ducting effects in a packet of curved nonlinear internal waves in shallow water is presented. Sound propagation roughly along the crests of the waves is simulated with a three-dimensional parabolic equation computational code, and the results are compared to measured propagation along fixed 3 and 6 km source/receiver paths. The measurements were made on the shelf of the South China Sea northeast of Tung-Sha Island. Construction of the time-varying three-dimensional sound-speed fields used in the modeling simulations was guided by environmental data collected concurrently with the acoustic data...
September 2011: Journal of the Acoustical Society of America
Itziar Oteo, John C Lukas, Nerea Leal, Elena Suarez, Andres Valdivieso, Mikel Gastaca, Jorge Ortiz de Urbina, Rosario Calvo
PURPOSE: To explore the main factors that make it difficult to empirically monitor tacrolimus (TAC) in the early period post-liver transplantation (LTx), with a specific focus on those aspects related to patient idiosyncrasy and clinical status as well as to the pharmacokinetic (PK) assumptions on which drug individualization in clinical practice is based. METHODS: Retrospective monitoring data from 75 de novo liver transplant patients treated with twice daily with TAC and followed for up to 15 days were analyzed...
July 2011: European Journal of Clinical Pharmacology
Behfar Moghaddam, M Habib Ali, Jitinder Wilkhu, Daniel J Kirby, Afzal R Mohammed, Qinguo Zheng, Yvonne Perrie
The study of surfactant monolayers is certainly not a new technique, but the application of monolayer studies to elucidate controlling factors in liposome design remains an underutilised resource. Using a Langmuir-Blodgett trough, pure and mixed lipid monolayers can be investigated, both for their interactions within the monolayer, and for interfacial interactions with drugs in the aqueous sub-phase. Despite these monolayers effectively being only half a bilayer, with a flat rather than curved structure, information from these studies can be effectively translated into liposomal systems...
September 30, 2011: International Journal of Pharmaceutics
Susan E Tett, Franck Saint-Marcoux, Christine E Staatz, Merce Brunet, Alexander A Vinks, Masatomo Miura, Pierre Marquet, Dirk R Kuypers, Teun van Gelder, Dario Cattaneo
UNLABELLED: This article summarizes part of a consensus meeting about mycophenolate (MPA) therapeutic drug monitoring held in Rome under the auspices of The Transplantation Society in November 2008 (Clin J Am Soc Nephrol. 2010;5:341-358). This part of the meeting focused on the clinical pharmacokinetics of MPA and included discussion on how to measure MPA (active drug) exposure and the differences between the currently available formulations. SUMMARY POINTS: Because of variability in the dose-concentration relationship, MPA exposure should be measured and doses should be adjusted accordingly to achieve optimal clinical outcomes...
April 2011: Transplantation Reviews
Peter A Williamson, Philip M Short, Karine L Clearie, Sriram Vaidyanathan, Thomas C Fardon, Laura J Howaniec, Brian J Lipworth
BACKGROUND: Lowest receptor occupancy for a drug occurs at trough prior to the next dose. Previous studies have focused on the effects of triple therapy at peak dose intervals using forced expiratory maneuvers. Impulse oscillometry (IOS) and body plethysmography (PLETH) are more sensitive than spirometry to assess inhaled therapies in COPD. METHODS: Nineteen patients with COPD (FEV(1)/FVC ratio < 0.7; FEV(1) < 60%) completed a double-blind randomized crossover trial of tiotropium 18 microg/d or placebo for 2 weeks each, with a 1-week washout...
2010: Chest
Masatomo Miura, Shigeru Satoh, Takenori Niioka, Hideaki Kagaya, Mitsuru Saito, Makoto Hayakari, Tomonori Habuchi, Toshio Suzuki
The aim of this study was to develop a limited sampling strategy to allow the simultaneous estimation of the area under the concentration-time curves (AUCs) of tacrolimus and mycophenolic acid (MPA), the active metabolite of the prodrug mycophenolate mofetil, using a small number of samples from patients undergoing renal transplantation. Fifty Japanese patients were enrolled. On day 28 after transplantation, samples were collected just before and 1, 2, 3, 4, 6, 9, and 12 hours after tacrolimus and mycophenolate mofetil administration at 9:00 am and 9:00 pm...
February 2008: Therapeutic Drug Monitoring
Gene D Morse, Margaret A Fischl, Mark J Shelton, Steve R Cox, Leslie Thompson, Andrew A Della-Coletta, William W Freimuth
OBJECTIVE: In a prior single-dose study that examined the effect of food on delavirdine pharmacokinetics in healthy volunteers, the absorption of delavirdine mesylate was delayed and the area under the curve was reduced by 26% in the presence of food. Since the complex, nonlinear pharmacokinetics of delavirdine do not permit a simple extrapolation of the results of a single-dose study to steady state, the present multiple-dose study was performed. PATIENTS AND STUDY DESIGN: Thirteen stable patients with HIV-1 infection (two females, 11 males; CD4 count range 124-588 cells/mm(3)) completed a randomised, crossover study in which subjects received two 14-day treatments with delavirdine mesylate 400mg every 8 hours...
2003: Clinical Drug Investigation
Dag Nyholm
Pharmacotherapy for Parkinson's disease is focused on dopaminergic drugs, mainly the dopamine precursor levodopa and dopamine receptor agonists. The elimination half-life (t(1/2)) of levodopa from plasma (in combination with a decarboxylase inhibitor) of about 1.5 hours becomes more influential as the disease progresses. The long-duration of response to levodopa, which is evident in early Parkinson's disease, diminishes and after a few years of treatment motor performance is closely correlated to the fluctuating plasma concentrations of levodopa...
2006: Clinical Pharmacokinetics
Dirk R J Kuypers
Therapeutic drug monitoring (TDM) of immunosuppressive therapy is becoming an increasingly complex matter as the number of compounds and their respective combinations are continuously expanding. Unfortunately, in clinical practice, monitoring predose trough blood concentrations is often not sufficient for guiding optimal long-term dosing of these drugs. The excellent short-term results obtained nowadays in renal transplantation confer a misleading feeling of safety despite the fact that long-term results have not substantially improved, definitely not to a point where longer graft survival could counteract the increasing need for transplant organs and less toxicity and side-effects could ameliorate patient survival...
February 2005: Transplant International: Official Journal of the European Society for Organ Transplantation
Lutz T Weber, Victor W Armstrong, Maria Shipkova, Reinhard Feneberg, Manfred Wiesel, Otto Mehls, Lothar B Zimmerhackl, Michael Oellerich, Burkhard Tönshoff
The current focus of cyclosporin A (CsA) monitoring in adult transplantation for optimized immunosuppression is on the early portion of the CsA area under the concentration-time curve (AUC), particularly in the first 4 hours postdose, designated as AUC(0-4), and on the blood concentration 2 hours postdose (C2) as a highly predictive marker for AUC(0-4). Because data in pediatric patients are scarce, full-time (12 hours) and absorption profiles of CsA were analyzed in relation to CsA effectiveness in 61 pediatric renal transplant recipients aged 3...
August 2004: Therapeutic Drug Monitoring
S Vítko, O Viklický
Cyclosporine (CsA), introduced as an immunosuppressive agent in the 1980s, quickly become the first-line treatment in organ transplantation. However, these improvements were associated with an increased incidence of renal dysfunction. CsA causes histopathological changes in renal transplants that are often difficult to distinguish from other processes, especially chronic allograft nephropathy. Enhanced angiotensin II, transforming growth factor-beta, and vascular endothelial growth factor expression together with down-regulation of nitric oxide synthesis may play roles in chronic CsA nephropathy...
March 2004: Transplantation Proceedings
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