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Children and pharmacokinetics

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https://www.readbyqxmd.com/read/29782406/population-pharmacokinetics-and-pharmacodynamics-of-dexmedetomidine-in-children-undergoing-ambulatory-surgery
#1
María-Gabriela Pérez-Guillé, Alejandra Toledo-López, Liliana Rivera-Espinosa, Radames Alemon-Medina, Chiharu Murata, Ismael Lares-Asseff, Juan Luis Chávez-Pacheco, Josefina Gómez-Garduño, Ana-Lilia Zamora Gutiérrez, Claudia Orozco-Galicia, Karina Ramírez-Morales, Gustavo Lugo-Goytia
BACKGROUND: Dexmedetomidine (DEX) is an α-2 adrenergic agonist with sedative and analgesic properties. Although not approved for pediatric use by the Food and Drug Administration, DEX is increasingly used in pediatric anesthesia and critical care. However, very limited information is available regarding the pharmacokinetics of DEX in children. The aim of this study was to investigate DEX pharmacokinetics and pharmacodynamics (PK-PD) in Mexican children 2-18 years of age who were undergoing outpatient surgical procedures...
May 17, 2018: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/29777528/state-of-the-art-review-on-physiologically-based-pharmacokinetic-modeling-in-pediatric-drug-development
#2
REVIEW
Venkata Yellepeddi, Joseph Rower, Xiaoxi Liu, Shaun Kumar, Jahidur Rashid, Catherine M T Sherwin
Physiologically based pharmacokinetic modeling and simulation is an important tool for predicting the pharmacokinetics, pharmacodynamics, and safety of drugs in pediatrics. Physiologically based pharmacokinetic modeling is applied in pediatric drug development for first-time-in-pediatric dose selection, simulation-based trial design, correlation with target organ toxicities, risk assessment by investigating possible drug-drug interactions, real-time assessment of pharmacokinetic-safety relationships, and assessment of non-systemic biodistribution targets...
May 18, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29770901/factors-impacting-unbound-vancomycin-concentrations-in-neonates-and-young-infants
#3
Anne Smits, Steven Pauwels, Matthijs Oyaert, Nele Peersman, Isabel Spriet, Veroniek Saegeman, Karel Allegaert
Vancomycin pharmacokinetic (PK) and pharmacodynamic (PD) data in neonates are based on total concentrations. However, only unbound vancomycin is pharmacologically active. The objective was to determine vancomycin protein binding and the covariates impacting unbound vancomycin concentration in neonates and young infants. In neonates and young infants to whom vancomycin was administered intermittently for medical indications, total and unbound vancomycin plasma concentrations were determined using LC-MS/MS. Sampling occurred randomly during vancomycin exposure, covering a broad range of concentrations...
May 16, 2018: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/29768231/enhanced-stability-of-l-asparaginase-by-its-bioconjugation-to-poly-styrene-co-maleic-acid-and-ecoflex-nanoparticles
#4
Jaleh Varshosaz, Negin Anvari
Acute lymphoblastic leukemia (ALL) is the white blood cell cancer in children. L-asparaginase (L-ASNase) is one of the first drugs used in ALL treatment. Anti-tumor activity of L-ASNase is not specific and indicates limited stability in different biological environments, in addition to its quick clearance from blood. The purpose of the present study was to achieve a new L-ASNase polymer bioconjugate to improve pharmacokinetic, increase half-life and stability of the enzyme. The conjugations were achieved by the cross-linking agent of 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide (EDC) which activates the carboxylic acid groups of polymeric nanoparticles to create amide bond...
June 2018: IET Nanobiotechnology
https://www.readbyqxmd.com/read/29761538/pharmacokinetics-of-cefuroxime-in-infants-and-neonates-undergoing-cardiac-surgery
#5
R Gertler, M Gruber, G Wiesner, S Grassin-Delyle, S Urien, P Tassani-Prell, K Martin
AIM: Very little data exist regarding the effect of cardiopulmonary bypass (CPB) on cefuroxime (CXM) pharmacokinetics in children less than one year of age. METHODS: 50 mg kg-1 CXM iv after induction were followed by 75 mg kg-1 into the CPB circuit. In 42 patients undergoing cardiac surgery 15 to 20 samples were obtained between 5 and 360 min after each dose. Total CXM concentrations were measured by high-performance liquid chromatography and a PK/PD modelling was performed...
May 14, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29758291/dr-elliot-f-ellis-initiating-personalized-asthma-management-in-children
#6
Stanley J Szefler
Elliot F. Ellis is indeed a giant in the field of allergy and immunology. From his leadership role in developing a pediatric allergy and immunology fellowship at National Jewish Health and his seminal work in theophylline pharmacokinetics, he trained many excellent clinicians and researchers. He assumed the role of Chair of Pediatrics at the Children's Hospital of Buffalo in 1974 and transformed that training program in pediatrics to a top-rated program in the country along with his own training program in allergy and immunology...
May 11, 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29757380/simultaneous-population-pharmacokinetic-modelling-of-plasma-and-intracellular-pbmc-miltefosine-concentrations-in-new-world-cutaneous-leishmaniasis-and-exploration-of-exposure-response-relationships
#7
Anke E Kip, María Del Mar Castro, Maria Adelaida Gomez, Alexandra Cossio, Jan H M Schellens, Jos H Beijnen, Nancy Gore Saravia, Thomas P C Dorlo
Objectives: Leishmania parasites reside within macrophages and the direct target of antileishmanial drugs is therefore intracellular. We aimed to characterize the intracellular PBMC miltefosine kinetics by developing a population pharmacokinetic (PK) model simultaneously describing plasma and intracellular PBMC pharmacokinetics. Furthermore, we explored exposure-response relationships and simulated alternative dosing regimens. Patients and methods: A population PK model was developed with NONMEM, based on 339 plasma and 194 PBMC miltefosine concentrations from Colombian cutaneous leishmaniasis patients [29 children (2-12 years old) and 22 adults] receiving 1...
May 10, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29753157/treosulfan-fludarabine-and-low-dose-total-body-irradiation-for-children-and-young-adults-with-acute-myeloid-leukemia-or-myelodysplastic-syndrome-undergoing-allogeneic-hematopoietic-cell-transplantation-a-prospective-phase-ii-trial-of-the-pediatric-blood-and
#8
Eneida R Nemecek, Ralf A Hilger, Alexia Adams, Bronwen E Shaw, Deidre Kiefer, Jennifer Le-Rademacher, John E Levine, Gregory Yanik, Wing Leung, Julie-An Talano, Paul Haut, David Delgado, Neena Kapoor, Aleksandra Petrovic, Roberta Adams, Rabi Hanna, Hemalatha Rangarajan, Jignesh Dalal, Joseph Chewning, Michael R Verneris, Stacy Epstein, Lauri Burroughs, Evelio D Perez-Albuerne, Michael A Pulsipher, Colleen Delaney
This multicenter study evaluated a treosulfan-based regimen in children and young adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplant (HCT). Forty patients with median age 11 years (1-19) underwent allogeneic HCT for AML in first (n=18), second (n=11), third or greater remission (n=3); or MDS (n=8) using bone marrow (n=25), peripheral blood stem cells (n=5) or cord blood (n=9). The regimen consisted of body surface area (BSA)-based treosulfan 10 g/m2 /day (BSA ≤ 0...
May 9, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29751121/evaluation-of-dried-blood-spot-sampling-for-pharmacokinetic-research-and-therapeutic-drug-monitoring-of-anti-tuberculosis-drugs-in-children
#9
Lisa C Martial, Jordy Kerkhoff, Nilza Martinez, Mabel Rodríguez, Rosarito Coronel, Gladys Molinas, Myriam Roman, Roscio Gomez, Sarita Aguirre, Erwin Jongedijk, Justine Huisman, Daan J Touw, Domingo Pérez, Gilberto Chaparro, Felipe Gonzalez, Rob E Aarnoutse, Jan-Willem Alffenaar, Cecile Magis-Escurra
BACKGROUND: Dried blood spot sampling (DBS) for pharmacokinetic (PK) studies and Therapeutic Drug Monitoring has unique advantages over venous sampling. We aimed to evaluate a DBS method for first-line anti-TB drugs in children, implemented DBS to assess PK parameters. METHODS: Paraguayan children were treated according to the revised paediatric WHO dosing scheme. A PK curve was performed both with DBS and conventional venous sampling for rifampicin, pyrazinamide and ethambutol...
May 8, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29750317/mycophenolate-mofetil-for-sustained-remission-in-nephrotic-syndrome
#10
Uwe Querfeld, Lutz T Weber
The clinical application of mycophenolate mofetil (MMF) has significantly widened beyond the prophylaxis of acute and chronic rejections in solid organ transplantation. MMF has been recognized as an excellent treatment option in many immunologic glomerulopathies. For children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS) experiencing steroid toxicity, MMF has been recommended as a steroid-sparing drug. Uncontrolled studies in patients with FRNS and SDSN have shown that many patients can achieve sustained remission of proteinuria with MMF monotherapy...
May 11, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29748932/increased-metformin-clearance-in-overweight-and-obese-adolescents-a-pharmacokinetic-substudy-of-a-randomized-controlled-trial
#11
Anne van Rongen, Marloes P van der Aa, Maja Matic, Ron H N van Schaik, Vera H M Deneer, Marja M van der Vorst, Catherijne A J Knibbe
BACKGROUND: In view of the increased use of metformin in obese adolescents, the aim of this study was to determine the pharmacokinetics of metformin in overweight and obese adolescents. METHODS: In overweight and obese adolescents receiving metformin 500 or 1000 mg twice daily for 37 weeks during a clinical trial, blood samples were collected over 8 h during an oral glucose tolerance test. Population pharmacokinetic modeling was performed using NONMEM. RESULTS: Data for 22 overweight and obese adolescents with a mean total body weight (TBW) of 79...
May 10, 2018: Paediatric Drugs
https://www.readbyqxmd.com/read/29746901/epinephrine-auto-injectors-and-anaphylaxis-challenges-of-dose-depth-and-device
#12
REVIEW
Julie Brown
OBJECTIVES: 1. To review epinephrine dosing, site and route of administration, focusing on special populations (patients weighing less that 15 kg, and obese patients). 2. To discuss storage and delivery of epinephrine in pre-hospital and hospital settings. DATA SOURCES: Review of published literature. STUDY SELECTION: Relevancy. RESULTS: The recommended 0.01 mg/kg (max 0.3-0.5 mg) epinephrine dose in anaphylaxis is based on limited pharmacokinetic data in healthy volunteers...
May 7, 2018: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/29744900/pharmacokinetics-and-safety-of-fluconazole-and-micafungin-in-neonates-with-systemic-candidiasis-a-randomized-open-label-clinical-trial
#13
S Leroux, E Jacqz Aigrain, V Elie, F Legrand, C Barin-Le Guellec, B Aurich, V Biran, B Dusang, S Goudjil, S Coopman, R Garcia Sanchez, W Zhao, P Manzoni
AIMS: Pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear inconsistent with the emerging scientific evidence. Limited information is available on their safety profile in neonates. Our objective was to study population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. METHODS: Neonates were randomized 1:1 to fluconazole (loading dose 25mg/kg; maintenance dose 12 or 20mg/kg/day for infants <30 or ≥ 30 weeks corrected gestational age) or micafungin (loading dose 15mg/kg/day; maintenance dose 10mg/kg/day)...
May 10, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29742643/pharmacokinetic-monitoring-of-vancomycin-in-cystic-fibrosis-is-it-time-to-move-past-trough-concentrations
#14
Nicholas M Fusco, William A Prescott, Calvin J Meaney
BACKGROUND: A correlation between vancomycin trough concentrations (VTC) and area under the curve (AUC) to minimum inhibitory concentration (MIC) ratio (AUC/MIC) has not been established in children/adolescents with cystic fibrosis (CF). The primary objective of this study was to determine the correlation between measured VTCs and AUC/MIC using population-based pharmacokinetics. METHODS: A retrospective cohort study of children/adolescents diagnosed with CF, age 6 to < 18 years, treated with vancomycin (VAN) for methicillin-resistant Staphylococcus aureus (MRSA) infection was conducted...
May 4, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29737521/age-and-genotype-dependent-variability-in-the-protein-abundance-and-activity-of-six-major-uridine-diphosphate-glucuronosyltransferases-in-human-liver
#15
Deepak Kumar Bhatt, Aanchal Mehrotra, Andrea Gaedigk, Revathi Chapa, Abdul Basit, Haeyoung Zhang, Prachi Choudhari, Mikael Boberg, Robin E Pearce, Roger Gaedigk, Ulrich Broeckel, J Steven Leeder, Bhagwat Prasad
The ontogeny of hepatic uridine diphosphate-glucuronosyltransferases (UGTs) was investigated by LC-MS/MS proteomics to determine UGT protein abundance in human liver microsomes isolated from 136 pediatric (0-18 years) and 35 adult (age 18-67 years) donors. Microsomal protein abundances of UGT1A1, UGT1A4, UGT1A6, UGT1A9, UGT2B7 and UGT2B15 increased by ∼8, 55, 35, 33, 8 and 3-fold from neonates to adults, respectively. The estimated age at which 50% of the adult protein abundance is observed for UGT isoforms was between 2...
May 8, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29732182/drugs-pharmacokinetics-during-veno-venous-extracorporeal-membrane-oxygenation-in-pediatrics
#16
REVIEW
Matteo Di Nardo, Enno Diederick Wildschut
Data evaluating pharmacokinetic/pharmacodynamic (PK/PD) aspect in the pediatric population are scarce especially regarding the pediatric intensive care unit. Dosing of frequently used drugs (sedatives, analgesics, antibiotics and cardiovascular drugs) are mainly based on non "pediatric intensive care unit (PICU)" patients, and sometimes are translated from adult patients. Among PICU patients, the most complex patients are the ones who are critically ill and are receiving mechanical circulatory/respiratory support for cardiac and/or respiratory failure...
March 2018: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29728755/ed50-of-remifentanil-for-providing-excellent-intubating-conditions-when-co-administered-with-a-single-standard-dose-of-propofol-without-the-use-of-muscle-relaxants-in-children-dose-finding-clinical-trial
#17
Andre Hideo Ono, Thiago Rocha Moura, Cátia Sousa Govêia, Gabriel Magalhães Nunes Guimarães, Luís Cláudio de Araújo Ladeira, Helga Bezerra Gomes da Silva
PURPOSE: Previous studies evidenced that orotracheal intubation without neuromuscular blockers is feasible in children and has some potential advantages. Remifentanil has favorable pharmacodynamic and pharmacokinetic properties as an opioid for orotracheal intubation, but its dose for excellent intubation conditions when co-administered with propofol has not been established. This study was designed to find the minimum effective dose of remifentanil for excellent intubation conditions of children when co-administered with propofol, without neuromuscular relaxant drugs...
May 4, 2018: Journal of Anesthesia
https://www.readbyqxmd.com/read/29721323/inconsistencies-in-dosage-practice-in-children-with-overweight-or-obesity-a-retrospective-cohort-study
#18
Christina Gade, Hanne R Christensen, Kim P Dalhoff, Jens Christian Holm, Helle Holst
Obesity can affect the pharmacokinetics of most drugs, which may result in under- or overdosing if traditional pediatric dosing strategies are used. To investigate currently applied dosage strategies in children with overweight or obesity (overweight/obesity), in a clinical treatment facility. In particular, whether dosing guidelines were available and metrics of body size applied. A retrospective cohort study of 200 patients admitted to the Danish Children's Obesity Clinic. Data were collected from 2007 to 2015...
June 2018: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/29720909/use-of-individual-pharmacokinetics-to-improve-time-to-therapeutic-vancomycin-trough-in-pediatric-oncology-patients
#19
Calvin L Miller, S Alexander Winans, John J Veillette, Steven C Forland
OBJECTIVE: Optimization of vancomycin dosing is difficult in children, given rapid drug clearance and patient heterogeneity. We sought to evaluate the impact of dosing using individual pharmacokinetic parameters on time to goal trough concentration in pediatric oncology patients. METHODS: A retrospective review was conducted to assess vancomycin dosing in the pediatric oncology unit at Loma Linda University Children's Hospital between January 2013 and August 2013 (standard dosing group [SDG])...
March 2018: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29719113/a-phase-1-study-of-eribulin-mesylate-e7389-a-novel-microtubule-targeting-chemotherapeutic-agent-in-children-with-refractory-or-recurrent-solid-tumors-a-children-s-oncology-group-phase-1-consortium-study-advl1314
#20
Eric S Schafer, Rachel E Rau, Stacey Berg, Xiaowei Liu, Charles G Minard, David D'Adamo, Rachael Scott, Larisa Reyderman, Gresel Martinez, Sandhya Devarajan, Joel M Reid, Elizabeth Fox, Brenda J Weigel, Susan M Blaney
BACKGROUND: Eribulin mesylate is a novel anticancer agent that inhibits microtubule growth, without effects on shortening, and promotes nonproductive tubulin aggregate formation. We performed a phase 1 trial to determine the dose-limiting toxicities (DLTs), maximum tolerated or recommended phase 2 dose (MTD/RP2D), and pharmacokinetics (PK) of eribulin in children with refractory or recurrent solid (excluding central nervous system) tumors. METHODS: Eribulin was administered intravenously on days 1 and 8 in 21-day cycles...
May 2, 2018: Pediatric Blood & Cancer
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