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Children and pharmacokinetics

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https://www.readbyqxmd.com/read/29330781/a-review-of-the-methods-and-associated-mathematical-models-used-in-the-measurement-of-fat-free-mass
#1
REVIEW
Jaydeep Sinha, Stephen B Duffull, Hesham S Al-Sallami
Fat-free mass (FFM) represents the lean component of the body devoid of fat. It has been shown to be a useful predictor of drug dose requirements, particularly in obesity where the excess fat mass does not contribute to drug clearance. However, measuring FFM involves complex and/or expensive experimental methodologies that preclude their use in routine clinical practice. Thus, models to predict FFM from readily measurable variables, such as body weight and height, have been developed and are used in both population pharmacokinetic modelling and clinical practice...
January 12, 2018: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/29306656/association-between-a-microrna-binding-site-polymorphism-in-slco1a2-and-the-risk-of-delayed-methotrexate-elimination-in-chinese-children-with-acute-lymphoblastic-leukemia
#2
Shu-Mei Wang, Wei-Xin Zeng, Wan-Shui Wu, Lu-Lu Sun, Dan Yan
Organic anion-transporting polypeptide 1A2 (OATP1A2) is involved in the cellular uptake of methotrexate (MTX). Genetic variation in solute carrier organic anion transporter family member 1A2 (SLCO1A2, the coding gene of OATP1A2) has important implications for the elimination of MTX. We investigated the association between a microRNA (miRNA) binding site polymorphism (rs4149009 G > A) in the 3'-untranslated region (3'-UTR) of SLCO1A2 with the serum MTX concentrations in Chinese children with acute lymphoblastic leukemia (ALL)...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29301833/establishing-a-preclinical-multidisciplinary-board-for-brain-tumors
#3
Birgit Nimmervoll, Nidal Boulos, Brandon M Bianski, Jason Dapper, Michael DeCuypere, Anang A Shelat, Sabrina Terranova, Hope Elizabeth Terhune, Amar Gajjar, Yogesh T Patel, Burgess B Freeman, Arzu Onar-Thomas, Clinton F Stewart, Martine F Roussel, R Kiplin Guy, Thomas E Merchant, Christopher Calabrese, Karen D Wright, Richard J Gilbertson
PURPOSE: Curing all children with brain tumors will require an understanding of how each subtype responds to conventional treatments and how best to combine existing and novel therapies.  It is extremely challenging to acquire this knowledge in the clinic alone, especially among patients with rare tumors.  Therefore, we developed a preclinical brain tumor platform to test combinations of conventional and novel therapies in a manner that closely recapitulates clinic trials.  Experimental Design: A multidisciplinary team was established to design and conduct neurosurgical, fractionated radiotherapy and chemotherapy studies, alone or in combination, in accurate mouse models of supratentorial ependymoma (SEP) subtypes and choroid plexus carcinoma (CPC)...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29290748/therapeutic-drug-monitoring-of-prolonged-infusion-aztreonam-for-multi-drug-resistant-pseudomonas-aeruginosa-a-case-report
#4
Jeffrey J Cies, Richard J LaCoursiere, Wayne S Moore, Arun Chopra
Aztreonam, a broad-spectrum monobactam, is typically reserved for multidrug resistant (MDR) infections. Pharmacokinetic (PK) data to guide dosing in children, however, are limited to healthy volunteers or nonintensive care unit (ICU) patients. Impaired antibiotic delivery into tissue remains a major concern and may explain the high morbidity and mortality associated with MDR infections. Therefore, evaluating the PK changes in pediatric ICU patients is necessary to elucidate the most appropriate antimicrobial regimen...
November 2017: Journal of Pediatric Pharmacology and Therapeutics: JPPT: the Official Journal of PPAG
https://www.readbyqxmd.com/read/29290236/antimicrobial-treatment-of-infrequent-bacterial-species-isolated-in-children
#5
R Cohen, L de Pontual, Y Gillet, J Raymond
This section summarizes the empirical antimicrobial treatment according to the less frequent bacterial species responsible for infection whether community-acquired or nosocomial. It specifies their role in diseases and the recommended antibiotics, taking into account their natural and most common acquired resistance and the pharmacokinetic-pharmacodynamic parameters. The advice of an infectious disease specialist or bacteriologist is recommended.
December 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
https://www.readbyqxmd.com/read/29285245/a-population-pharmacokinetic-model-for-individualised-dosage-regimens-of-vancomycin-in-chinese-neonates-and-young-infants
#6
Lin Song, Cui-Yao He, Nan-Ge Yin, Fang Liu, Yun-Tao Jia, Yao Liu
Population pharmacokinetic (PPK) modelling is an easy and impartment method for estimating drug concentration for use inindividualized therapy, especially for young patients and to help protect drug-induced diseases. The purpose of this study was to develop a PPK model for effective dosing of vancomycin in Chinese neonates and young infants. The PPK modelling tool Phoenix® NLME™ was use to assess demographic and routine clinical pharmacokinetic (PK) data retrospectively collected for patients admitted to Children's Hospital of Chongqing Medical University between 2011 and 2016...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282674/correction-to-development-of-guanfacine-extended-release-dosing-strategies-in-children-and-adolescents-with-adhd-using-a-physiologically-based-pharmacokinetic-model-to-predict-drug-drug-interactions-with-moderate-cyp3a4-inhibitors-or-inducers
#7
Aiqun Li, Karen Yeo, Devin Welty, Haojing Rong
The article "Development of Guanfacine Extended-Release Dosing Strategies in Children and Adolescents with ADHD Using a PhysiologicallyBased Pharmacokinetic Model to Predict Drug-Drug Interactions with Moderate CYP3A4 Inhibitors or Inducers", written by Aiqun Li, Karen Yeo, Devin Welty, Haojing Rong, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 02nd November, 2017 without open access.
December 28, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/29282364/mir-pharmacogenetics-of-vincristine-and-peripheral-neurotoxicity-in-childhood-b-cell-acute-lymphoblastic-leukemia
#8
Ángela Gutierrez-Camino, Maitane Umerez, Idoia Martin-Guerrero, Nagore García de Andoin, Borja Santos, Ana Sastre, Aizpea Echebarria-Barona, Itziar Astigarraga, Aurora Navajas, Africa Garcia-Orad
Vincristine (VCR), an important component of childhood acute lymphoblastic leukemia (ALL) therapy, can cause sensory and motor neurotoxicity. This neurotoxicity could lead to dose reduction or treatment discontinuation, which could in turn reduce survival. In this line, several studies associated peripheral neurotoxicity and polymorphisms in genes involved in pharmacokinetics (PK) and pharmacodynamics (PD) of VCR. Nowadays, it is well known that these genes are regulated by microRNAs (miRNAs) and SNPs in miRNAs could modify their levels or function...
December 27, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/29282090/pharmacokinetic-and-safety-profile-of-tofacitinib-in-children-with-polyarticular-course-juvenile-idiopathic-arthritis-results-of-a-phase-1-open-label-multicenter-study
#9
Nicolino Ruperto, Hermine I Brunner, Zbigniew Zuber, Nikolay Tzaribachev, Daniel J Kingsbury, Ivan Foeldvari, Gerd Horneff, Elzbieta Smolewska, Richard K Vehe, Anasuya Hazra, Rong Wang, Charles A Mebus, Christine Alvey, Manisha Lamba, Sriram Krishnaswami, Thomas C Stock, Min Wang, Ricardo Suehiro, Alberto Martini, Daniel J Lovell
BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease and a leading cause of childhood disability. The objective of this study was to characterize the PK, safety, and taste acceptability of tofacitinib in patients with JIA. METHODS: This Phase 1, open-label, multiple-dose (twice daily [BID] for 5 days) study of tofacitinib in patients with active (≥ 5 joints) polyarticular course JIA was conducted from March 2013-December 2015...
December 28, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/29277665/tacrolimus-an-updated-review-on-delivering-strategies-for-multifarious-diseases
#10
REVIEW
Divya Dheer, Jyoti, Prem N Gupta, Ravi Shankar
From the current trends, tacrolimus (TAC) has become an important therapeutic option for the optimal individualization of immunosuppressive therapy especially in case of transplant recipients. TAC is used most frequently in comparison to other immunosuppressants because it offers better safety profile with increased long-term survival in patients especially in children and adolescents. This drug has developed an immense interest in the research field owing to its potential pharmacological scope but due to its poor water solubility, need of concomitant steroids and higher incidences of nephrotoxicity, there comes a need for future research to minimize such limitations and decipher maximum use of the drug...
December 22, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29275265/anesthetic-and-pharmacologic-considerations-in-perioperative-care-of-obese-children
#11
REVIEW
Vidya Chidambaran, Anurag Tewari, Mohamed Mahmoud
PURPOSE: Anesthetic management of obese pediatric patients is challenging. With increasing prevalence of childhood obesity, more severely obese children with comorbidities present for surgery every day. The purpose of this review is to provide an up-to-date comprehensive narrative review on the impact of pathophysiological changes imposed by pediatric obesity on the perioperative management of obese children, especially drug dosing. This knowledge is necessary to provide safe delivery of anesthesia for severely obese children...
December 21, 2017: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/29247538/narrative-review-shows-that-the-short-term-use-of-ketorolac-is-safe-and-effective-in-the-management-of-moderate-to-severe-pain-in-children
#12
REVIEW
Pierluigi Marzuillo, Lorenzo Calligaris, Stefano Amoroso, Egidio Barbi
In June 2013, the European Medicine Agency recommended limiting codeine use in paediatric patients, creating a void in managing moderate pain. We reviewed literature published in English (1985-June 2017) on the pharmacokinetic, pharmacodynamic and safety profile of ketorolac, a possible substitute for codeine and opioids, for treating moderate to severe pain. We found that gastrointestinal side effects were mainly reported with prolonged use, significant bleeding was reported in adenotonsillectomies and adverse renal effects appeared to be limited to patients with specific coexisting risk factors...
December 16, 2017: Acta Paediatrica
https://www.readbyqxmd.com/read/29247506/suboptimal-anti-tuberculosis-drug-concentrations-and-outcomes-in-small-and-hiv-coinfected-children-in-india-recommendations-for-dose-modifications
#13
Benjamin Guiastrennec, Geetha Ramachandran, Mats O Karlsson, A K Hemanth Kumar, Perumal Kannabiran Bhavani, N Poorana Gangadevi, Soumya Swaminathan, Amita Gupta, Kelly E Dooley, Radojka M Savic
This work aimed to evaluate the once-daily anti-tuberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin and pyrazinamide concentration-time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure-response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome...
December 16, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29240266/posaconazole-oral-dose-and-plasma-levels-in-pediatric-hematology-oncology-patients
#14
Edoardo Bruno Vicenzi, Elisabetta Calore, Nunzia Decembrino, Massimo Berger, Katia Perruccio, Francesca Carraro, Sara Rossin, Maria Caterina Putti, Mariadelfina Molinaro, Gloria Tridello, Simone Cesaro
BACKGROUND: Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole-oral-solution daily dosage/kg/body weight and trough plasma level. METHODS: 97 hematology-oncology pediatric patients with > 1 posaconazole plasma level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included. RESULTS: Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%)...
December 14, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/29238995/test-dose-pharmacokinetics-in-pediatric-patients-receiving-once-daily-iv-busulfan-conditioning-for-hematopoietic-stem-cell-transplant-a-reliable-approach
#15
Kristina M Brooks, Paul Jarosinski, Thomas Hughes, Elizabeth Kang, Nirali N Shah, John B Le Gall, Dennis D Hickstein, Suk See De Ravin, Jomy M George, Parag Kumar
Intravenous (IV) busulfan test dose pharmacokinetics (PK) has been shown to accurately predict once-daily dose requirements and improve outcomes in adult transplant patients, but there are limited data to support this approach in children. Test doses of busulfan ∼0.8 mg/kg were infused over 2 to 3 hours, followed by serial sampling to 4-6 hours postinfusion in pediatric hematopoietic stem cell transplant recipients (n = 5). Once-daily busulfan doses were calculated based on a myelosuppressive area under the concentration-time curve (AUC) target of ∼3700 to 4000 μmol·min/L and assumed dose-proportionality to the test dose...
December 14, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29235880/a-critical-review-of-physicochemical-properties-and-analytical-methods-applied-to-quantitative-determination-of-ebastine
#16
Rafael Giorgetti Frare, Anil Kumar Singh
Allergic diseases are the most common conditions in children and the second most frequent in adults. Currently, there are two well-defined generations of antihistamines, those belonging to first generation, with inherent side effects such as drowsiness and anticholinergic effects. These side effects are often attributed to their high lipophilicity and high affinity for brain H1 receptors. The ebastine is a modern antihistaminic drug belongs to the second generation and has lower lipophilicity, which diminish the undesirable side effects...
December 13, 2017: Critical Reviews in Analytical Chemistry
https://www.readbyqxmd.com/read/29229171/special-considerations-in-pediatric-kidney-transplantation
#17
REVIEW
Sean A Hebert, Rita D Swinford, David R Hall, Jason K Au, John S Bynon
Universally accepted as the treatment of choice for children needing renal replacement therapy, kidney transplantation affords children the opportunity for an improved quality of life over dialysis therapy. Immunologic and surgical advances over the last 15 years have improved the pediatric patient and kidney graft survival. Unique to pediatrics, congenital genitourinary anomalies are the most common primary diseases leading to kidney failure, many with urological issues. Early urological evaluation for post-transplant bladder dysfunction and emphasis on immunization adherence are the mainstays of pediatric pretransplant and post-transplant evaluations...
November 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29227461/population-pharmacokinetics-of-lopinavir-in-severely-malnourished-hiv-infected-children-and-the-effect-on-treatment-outcomes
#18
Moherndran Archary, Helen Mcllleron, Raziya Bobat, Phillip La Russa, Thobekile Sibaya, Lubbe Wiesner, Stefanie Hennig
BACKGROUND: In developing countries, malnutrition remains a common clinical syndrome at antiretroviral treatment (ART) initiation. Physiological changes due to malnutrition and during nutritional recovery could affect the pharmacokinetics of antiretroviral drugs. METHODS: HIV-infected children admitted with severe acute malnutrition were randomised to early or delayed initiation of lopinavir/ritonavir, abacavir and lamivudine using WHO weight-band dosage charts...
December 8, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29218501/evaluating-safety-reporting-in-paediatric-antibiotic-trials-2000-2016-a-systematic-review-and-meta-analysis
#19
REVIEW
Paola Pansa, Yingfen Hsia, Julia Bielicki, Irja Lutsar, A Sarah Walker, Mike Sharland, Laura Folgori
BACKGROUND: There are very few options to treat multidrug-resistant bacterial infections in children. A major barrier is the duration and complexity of regulatory trials of new antibiotics. Extrapolation of safety data from adult trials could facilitate drug development for children. OBJECTIVE: We performed a systematic review on the safety of antibiotic clinical trials (CTs) in children (0-18 years) to evaluate the overall quality of safety trials conducted in children and to determine if age-specific adverse events (AEs) could be identified for specific antibiotic classes...
December 7, 2017: Drugs
https://www.readbyqxmd.com/read/29216273/isoniazid-concentrations-in-hair-and-plasma-area-under-the-curve-exposure-among-children-with-tuberculosis
#20
Vidya Mave, Aarti Kinikar, Anju Kagal, Smita Nimkar, Hari Koli, Sultanat Khwaja, Renu Bharadwaj, Roy Gerona, Anita Wen, Geetha Ramachandran, Hemanth Kumar, Peter Bacchetti, Kelly E Dooley, Nikhil Gupte, Amita Gupta, Monica Gandhi
We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment...
2017: PloS One
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