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Children and pharmacokinetics

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https://www.readbyqxmd.com/read/28101656/off-label-use-of-antimicrobials-in-neonates-in-a-tertiary-children-s-hospital
#1
Niina Laine, Ann Marie Kaukonen, Kalle Hoppu, Marja Airaksinen, Harri Saxen
PURPOSE: Off-label (OL) use of drugs for hospitalized children is very common. OL use occurs especially in the youngest patients, neonates. This study focused on the OL use of antimicrobials in neonates. To our knowledge, only few studies have focused on the prevalence of OL use of antimicrobials in neonates. METHODS: We investigated the OL use of antimicrobials in neonates in a tertiary children's hospital. First, we investigated what were the most consumed OL antimicrobials in defined daily doses according to hospital's registry data from neonatal intensive care unit (NICU) during 2009-2014...
January 18, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28096535/genetics-of-ancestry-specific-risk-for-relapse-in-acute-lymphoblastic-leukemia
#2
S E Karol, E Larsen, C Cheng, X Cao, W Yang, L B Ramsey, C A Fernandez, J R McCorkle, S W Paugh, R J Autry, E Lopez-Lopez, B Diouf, S Jeha, C-H Pui, E A Raetz, N J Winick, W L Carroll, S P Hunger, M L Loh, M Devidas, W E Evans, J J Yang, M V Relling
The causes of individual relapses in children with acute lymphoblastic leukemia (ALL) remain incompletely understood. We evaluated the contribution of germline genetic factors to relapse in 2225 children treated on Children's Oncology Group trial AALL0232. We identified 302 germline single nucleotide polymorphisms (SNPs) associated with relapse after adjusting for treatment and ancestry and 715 additional SNPs associated with relapse in an ancestry-specific manner. We tested for replication of these relapse-associated SNPs in external data sets of antileukemic drug pharmacokinetics and pharmacodynamics and an independent clinical cohort...
January 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28079918/dose-evaluation-of-lamivudine-in-hiv-infected-children-aged-5%C3%A2-months-18%C3%A2-years-based-on-a-population-pharmacokinetic-analysis
#3
Esther J H Janssen, Diane E T Bastiaans, Pyry A J Välitalo, Annemarie M C van Rossum, Evelyne Jacqz-Aigrain, Hermione Lyall, Catherijne A J Knibbe, David M Burger
AIM: The objectives of this study were to characterise age-related changes in lamivudine pharmacokinetics in children and evaluate lamivudine exposure, followed by dose recommendations for subgroups in which target steady state AUC0-24h is not reached. METHODS: Population pharmacokinetic modelling was performed in NONMEM using data from two model building datasets and two external datasets (n = 180 (age 0.4-18 years, bodyweight 3.4-60.5 kg); 2,061 samples (median 12 per child); daily oral dose 60-300 mg (3...
January 12, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28079262/pediatric-obesity-pharmacokinetic-alterations-and-effects-on-antimicrobial-dosing
#4
Stephanie Natale, John Bradley, William Huy Nguyen, Tri Tran, Pamela Ny, Kirsten La, Eva Vivian, Jennifer Le
BACKGROUND: Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents, including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacill-tazobactam, tobramycin, vancomycin, and voriconazole, are presented...
January 12, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28078682/population-pharmacokinetics-of-intravenous-clonidine-for-sedation-during-pediatric-extracorporeal-membrane-oxygenation-ecmo-and-continuous-veno-venous-hemofiltration-cvvh
#5
Niina Kleiber, Ron A A Mathôt, Maurice J Ahsman, Enno D Wildschut, Dick Tibboel, Saskia N de Wildt
AIMS: Clonidine is used for sedation in the pediatric intensive care unit. Extracorporeal membrane oxygenation (ECMO) provides temporary support if respiratory and cardiac function is threatened. ECMO influences the pharmacokinetics of drugs. Clonidine during pediatric ECMO cannot be effectively titrated as PK data are lacking. The aim of this study is to describe clonidine PK in a particular ECMO system and propose dosing guidelines for children on this particular ECMO circuit. METHODS: All children below the age of 18 who received clonidine during ECMO were eligible...
January 12, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28078552/pediatric-development-of-bosentan-facilitated-by-modeling-and-simulation
#6
Jochen Zisowsky, Martine Géhin, Andjela Kusic-Pajic, Andreas Krause, Maurice Beghetti, Jasper Dingemanse
BACKGROUND: Bosentan is approved for use in adult patients with pulmonary arterial hypertension. The primary aim of the pharmacokinetic modeling was the provision of a systematic guidance for study design and enhanced understanding of pharmacokinetics across the entire pediatric age range. METHODS: A physiologically based pharmacokinetic model was developed for the pediatric population; starting from an adult model, the effects of body weight, age, and maturation of relevant metabolizing enzymes were incorporated to extrapolate the pharmacokinetics to children...
January 11, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/28074392/effect-of-cerebrolysin-on-gross-motor-function-of-children-with-cerebral-palsy-a-clinical-trial
#7
Jafar Nasiri, Faezeh Safavifar
Gross motor dysfunction is considered as the most challenging problem in cerebral palsy (CP). It is proven that improvement of gross motor function could reduce CP-related disabilities and provide better quality of life in this group of patients. Therefore, the aim of this trial is to evaluate the effectiveness of cerebrolysin (CBL) on gross motor function of children with CP who are undergoing treatment. In this clinical trial study, paediatric patients aged 18-75 months with spastic diplegic or quadriplegic cerebral palsy, who were under rehabilitation therapy, were selected and randomly allocated in control and CBL groups...
January 10, 2017: Acta Neurologica Belgica
https://www.readbyqxmd.com/read/28072872/population-pharmacokinetic-properties-of-piperaquine-in-falciparum-malaria-an-individual-participant-data-meta-analysis
#8
Richard M Hoglund, Lesley Workman, Michael D Edstein, Nguyen Xuan Thanh, Nguyen Ngoc Quang, Issaka Zongo, Jean Bosco Ouedraogo, Steffen Borrmann, Leah Mwai, Christian Nsanzabana, Ric N Price, Prabin Dahal, Nancy C Sambol, Sunil Parikh, Francois Nosten, Elizabeth A Ashley, Aung Pyae Phyo, Khin Maung Lwin, Rose McGready, Nicholas P J Day, Philippe J Guerin, Nicholas J White, Karen I Barnes, Joel Tarning
BACKGROUND: Artemisinin-based combination therapies (ACTs) are the mainstay of the current treatment of uncomplicated Plasmodium falciparum malaria, but ACT resistance is spreading across Southeast Asia. Dihydroartemisinin-piperaquine is one of the five ACTs currently recommended by the World Health Organization. Previous studies suggest that young children (<5 y) with malaria are under-dosed. This study utilised a population-based pharmacokinetic approach to optimise the antimalarial treatment regimen for piperaquine...
January 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28064419/pharmacokinetics-and-pharmacogenetics-of-carbamazepine-in-children
#9
Natasa Djordjevic, Slobodan M Jankovic, Jasmina R Milovanovic
Although carbamazepine is one of the oldest anticonvulsant drugs, it is still heavily utilized for treatment of epilepsy in children. The aim of this article was to review the current knowledge about pharmacokinetics and pharmacogenetics of carbamazepine in children. The literature for this review was systematically searched for in the MEDLINE and SCINDEKS databases. Oral bioavailability of carbamazepine in children is about 75-85%, and it is approximately 75-85% bound to plasma proteins. Apparent volume of distribution is 1...
January 7, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28064355/population-pharmacokinetic-models-of-lamotrigine-in-different-age-groups-of-chinese-children-with-epilepsy
#10
Zhong-Bin Zhang, Shuang-Min Ji, Ying Han, Li-Li Zang, Ying-Hui Wang, Wei Lu, Li Wang, Ye Wu
PURPOSE: The study aims to establish population pharmacokinetic (PPK) models of lamotrigine (LTG) in different age groups of epileptic children by nonlinear mixed effect modelling(NONMEM), and provide essential tools and theoretical basis for individualised optimal drug dose. METHODS: Cases of 473 epileptic children were divided into infant, toddler and preschool age (≤6 years) (n = 211), school age (6-12 years) (n = 171) and adolescence age (>12 years) (n = 81)...
January 7, 2017: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28060045/dalbavancin-pharmacokinetics-and-safety-in-children-3-months-to-11-years-of-age
#11
Daniel Gonzalez, John S Bradley, Jeffrey Blumer, Ram Yogev, Kevin M Watt, Laura P James, Debra L Palazzi, Varsha Bhatt-Mehta, Janice E Sullivan, Li Zhang, Jennifer Murphy, Xilla T Ussery, Sailaja Puttagunta, Michael W Dunne, Michael Cohen-Wolkowiez
BACKGROUND: Dalbavancin is a novel lipoglycopeptide antibiotic that has potent in vitro activity against Gram-positive microorganisms. METHODS: We performed a phase 1, open-label, multi-center study to investigate the pharmacokinetics (PK) and safety of a single-dose of intravenous dalbavancin in hospitalized pediatric subjects 3 months to 11 years of age. We combined these data with previously collected adolescent PK data and performed a population PK analysis...
January 3, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28060017/determinants-of-virological-outcome-and-adverse-events-in-african-children-treated-with-paediatric-nevirapine-fixed-dose-combination-tablets
#12
Andrzej Bienczak, Paolo Denti, Adrian Cook, Lubbe Wiesner, Veronica Mulenga, Cissy Kityo, Addy Kekitiinwa, Diana M Gibb, David Burger, A Sarah Walker, Helen Mcilleron
BACKGROUND: Nevirapine is the only non-nucleoside reverse transcriptase inhibitor currently available as a paediatric fixed-dose combination tablet and is widely used in African children. Nonetheless, the number of investigations into pharmacokinetic determinants of virological suppression in African children is limited and the predictive power of the current therapeutic range was never evaluated in this population, thereby limiting treatment optimisation. METHODS: We analysed data from 322 African children (aged 0...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28054971/the-development-of-urease-inhibitors-what-opportunities-exist-for-better-treatment-of-helicobacter-pylori-infection-in-children
#13
Sherif T S Hassan, Miroslava Šudomová
Stomach infection with Helicobacter pylori (H. pylori) causes severe gastroduodenal diseases in a large number of patients worldwide. The H. pylori infection breaks up in early childhood, persists lifelong if not treated, and is associated with chronic gastritis and an increased risk of peptic ulcers and gastric cancer. In recent years, the problem of drug-resistant strains has become a global concern that makes the treatment more complicated and the infection persistent at higher levels when the antibiotic treatment is stopped...
January 4, 2017: Children
https://www.readbyqxmd.com/read/28045861/pharmacokinetics-and-pharmacogenetics-of-ssris-during-pregnancy-an-observational-study
#14
Laura Pogliani, Felicia Stefania Falvella, Dario Cattaneo, Paola Pileri, Anna Flora Moscatiello, Stefania Cheli, Sara Baldelli, Valentina Fabiano, Irene Cetin, Emilio Clementi, Gianvincenzo Zuccotti
BACKGROUND: An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery. METHODS: Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered...
December 29, 2016: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28043170/impact-of-disease-drug-and-patient-adherence-on-the-effectiveness-of-antiviral-therapy-in-pediatric-hiv
#15
Chiara Piana, Meindert Danhof, Oscar Della Pasqua
Maintaining effective antiretroviral treatment for life is a major problem, in both resource-limited and resource-rich countries. Despite the progress observed in paediatric antiretroviral therapy, approximately 12% of children still experience treatment failure due to drug resistance, inadequate dosing and poor adherence. We explore the current status of antiretroviral therapy in children with focus on the interaction between disease, drug pharmacokinetics and patient behavior, all of which are strongly interconnected and determine treatment outcome...
January 3, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28040560/a-systematic-review-of-the-use-of-dosage-form-manipulation-to-obtain-required-doses-to-inform-use-of-manipulation-in-paediatric-practice
#16
REVIEW
Roberta H Richey, Clare Hughes, Jean V Craig, Utpal U Shah, James L Ford, Catrin E Barker, Matthew Peak, Anthony J Nunn, Mark A Turner
This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included...
December 28, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28039666/use-of-ceftaroline-fosamil-in-children-review-of-current-knowledge-and-its-application
#17
REVIEW
Juwon Yim, Leah M Molloy, Jason G Newland
Ceftaroline is a novel cephalosporin recently approved in children for treatment of acute bacterial skin and soft tissue infections and community-acquired bacterial pneumonia (CABP) caused by methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae and other susceptible bacteria. With a favorable tolerability profile and efficacy proven in pediatric patients and excellent in vitro activity against resistant Gram-positive and Gram-negative bacteria, ceftaroline may serve as a therapeutic option for polymicrobial infections, CABP caused by penicillin- and ceftriaxone-resistant S...
December 30, 2016: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/28033670/a-mini-review-of-non-parenteral-clonidine-preparations-for-paediatric-sedation
#18
REVIEW
Sara M Hanning, Mine Orlu Gul, Irmgard Toni, Antje Neubert, Catherine Tuleu
OBJECTIVE: To provide an overview of non-parenteral clonidine formulations and assess the feasibility of their use for paediatric sedation. METHODS: A literature search was conducted using electronic databases and a combination of search terms. Forty articles met the inclusion criteria. Publications were grouped into different dosage forms and assessed for their potential application for sedation of children in intensive care. KEY FINDINGS: Several routes of clonidine administration have been investigated for numerous indications in children, including perioperative sedation and analgesia...
December 29, 2016: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28032129/first-dose-and-steady-state-pharmacokinetics-of-orally-administered-crizotinib-in-children-with-solid-tumors-a-report-on-advl0912-from-the-children-s-oncology-group-phase-1-pilot-consortium
#19
Frank M Balis, Patrick A Thompson, Yael P Mosse, Susan M Blaney, Charles G Minard, Brenda J Weigel, Elizabeth Fox
PURPOSE: Characterize the pharmacokinetics of oral crizotinib in children with cancer. METHODS: Sixty-four children with solid tumors or anaplastic large-cell lymphoma (ALCL) enrolled on a phase 1/2 trial of the ALK, MET and ROS1 inhibitor, crizotinib, had pharmacokinetic sampling after the first dose (n = 15) or at steady state (n = 49). Dose levels studied were 100, 130, 165, 215, 280 and 365 mg/m(2)/dose administered twice daily. Two capsule and two oral liquid formulations were used over the course of the trial...
December 28, 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28030535/development-of-a-limited-sampling-strategy-for-the-estimation-of-exposure-to-high-dose-etoposide-after-intravenous-infusion-in-pediatric-patients
#20
Dorota Danielak, Joanna Sobiak, Jacek Wachowiak, Franciszek Główka, Maria Chrzanowska
BACKGROUND: Etoposide (VP-16), a podophylotoxin derivative, is used in conditioning regimens prior to allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children with acute lymphoblastic leukemia (ALL). The aim of this study was to develop a limited sampling strategy (LSS) suitable for the prediction of exposure to VP-16 defined as area-under-time-concentration curve (AUC). METHODS: The study included 28 pediatric patients with ALL, who were administered a 4h infusion of 60 mg/kg VP-16...
December 20, 2016: Therapeutic Drug Monitoring
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