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https://www.readbyqxmd.com/read/28230619/population-pharmacokinetics-of-topiramate-in-japanese-pediatric-and-adult-patients-with-epilepsy-using-routinely-monitored-data
#1
Masato Takeuchi, Ikuko Yano, Satoko Ito, Mitsuhiro Sugimoto, Shota Yamamoto, Atsushi Yonezawa, Akio Ikeda, Kazuo Matsubara
BACKGROUND: Topiramate is a second-generation antiepileptic drug used as monotherapy and adjunctive therapy in adults and children with partial seizures. A population pharmacokinetic analysis was performed to improve the topiramate dosage adjustment for individualized treatment. METHODS: Patients whose steady-state serum concentration of topiramate was routinely monitored at Kyoto University Hospital from April 2012 to March 2013 were included in the model-building data...
February 20, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28229374/effect-of-short-term-fasting-on-systemic-cytochrome-p450-mediated-drug-metabolism-in-healthy-subjects-a-randomized-controlled-crossover-study-using-a-cocktail-approach
#2
Laureen A Lammers, Roos Achterbergh, Ron H N van Schaik, Johannes A Romijn, Ron A A Mathôt
BACKGROUND AND OBJECTIVE: Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. METHODS: In a randomized, controlled, crossover trial, 12 healthy subjects received a single administration of a cytochrome P450 (CYP) probe cocktail, consisting of caffeine (CYP1A2), metoprolol (CYP2D6), midazolam (CYP3A4), omeprazole (CYP2C19) and warfarin (CYP2C9), on four occasions: an oral (1) and intravenous (2) administration after an overnight fast (control) and an oral (3) and intravenous (4) administration after 36 h of fasting...
February 22, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28196047/a-time-dependent-model-describes-methotrexate-elimination-and-supports-dynamic-modification-of-mrp2-abcc2-activity
#3
Jean-Baptiste Woillard, Jean Debord, Isabelle Benz-de-Bretagne, Franck Saint-Marcoux, Pascal Turlure, Stéphane Girault, Julie Abraham, Sylvain Choquet, Pierre Marquet, Chantal Barin-Le Guellec
BACKGROUND: MRP2/ABCC2, an efflux transporter expressed at the proximal renal tubule, is rate limiting for urine excretion of coproporphyrin (UCP) isomers I and III, translating in high UCP (I/(I+III)) ratio in MRP2-deficient patients presenting with the Dubin-Johnson Syndrome. MRP2 is also a major contributor to methotrexate (MTX) clearance. As MTX is both a substrate and an inhibitor of MRP2, time course of the concentrations of MTX in blood could induce functional modification of MRP2 over time, which in turn can modify its own elimination rate...
February 11, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28194623/comparison-of-non-compartmental-and-mixed-effect-modelling-methods-for-establishing-bioequivalence-for-the-case-of-two-compartment-kinetics-and-censored-concentrations
#4
Jim H Hughes, Richard N Upton, David J R Foster
Non-compartmental analysis (NCA) is regarded as the standard for establishing bioequivalence, despite its limitations and the existence of alternative methods such as non-linear mixed effects modelling (NLMEM). Comparisons of NCA and NLMEM in bioequivalence testing have been limited to drugs with one-compartment kinetics and have included a large number of different approaches. A simulation tool was developed with the ability to rapidly compare NCA and NLMEM methods in determining bioequivalence using both R and NONMEM and applied to a drug with two-compartment pharmacokinetics...
February 13, 2017: Journal of Pharmacokinetics and Pharmacodynamics
https://www.readbyqxmd.com/read/28177137/hypoalbuminemia-and-decreased-midazolam-clearance-in-terminally-ill-adult-patients-an-inflammatory-effect
#5
L G Franken, A D Masman, B C M de Winter, F P M Baar, D Tibboel, T van Gelder, B C P Koch, R A A Mathot
BACKGROUND AND OBJECTIVE: Midazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. Because of large inter-individual variability (IIV), however, the time it takes to achieve adequate sedation varies widely. It would therefore greatly improve clinical care if an individualised dose could be determined beforehand. To find clinically relevant parameters for dose individualisation we performed a pharmacokinetic study on midazolam, 1OH-midazolam (1-OH-M) and 1OH-midazolam-glucuronide (1-OH-MG) in terminally ill patients...
February 8, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28177130/a-population-pharmacokinetic-model-of-at9283-in-adults-and-children-to-predict-the-maximum-tolerated-dose-in-children-with-leukaemia
#6
Janna K Duong, Melanie J Griffin, Darren Hargrave, Josef Vormoor, David Edwards, Alan V Boddy
AIMS: AT9283 is used to treat patients with solid tumors and patients with leukaemia. However, the maximum tolerated dose (MTD) for children with leukaemia remains unknown due to early termination of the Phase I trial. The aim of this study was to develop a population model of AT9283 to describe the pharmacokinetics in adults and children and to estimate the MTD in children with leukaemia. METHODS: Data from Phase I dose-escalation studies in adults and children were used to build a population pharmacokinetic model (NONMEM v7...
February 8, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28168884/population-pharmacokinetics-and-pharmacodynamics-of-doripenem-in-obese-hospitalized-patients
#7
Eun Kyoung Chung, Megan R Fleming, S Christian Cheatham, Michael B Kays
BACKGROUND: Doripenem population pharmacokinetics and dosing recommendations are limited in obesity. OBJECTIVE: To evaluate the population pharmacokinetics and pharmacodynamics of doripenem in obese patients. METHODS: Hospitalized adults with a body mass index (BMI) ≥ 40 kg/m(2) or total body weight (TBW) ≥45.5 kg over their ideal body weight received doripenem 500 mg every 8 hours, infused over 1 hour. Population pharmacokinetic analyses were performed using NONMEM, and Monte Carlo simulations were performed for 5 intermittent and prolonged infusion dosing regimens to calculate probability of target attainment (PTA) at 40% and 100% fT>MIC (free drug concentrations above the minimum inhibitory concentration)...
March 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28167229/population-pharmacokinetics-model-of-thc-used-by-pulmonary-route-in-occasional-cannabis-smokers
#8
A Marsot, C Audebert, L Attolini, B Lacarelle, J Micallef, O Blin
Cannabis is the most widely used illegal drug in the world. Delta-9-tetrahydrocannabinol (THC) is the main source of the pharmacological effect. Some studies have been carried out and showed significant variability in the described models as the values of the estimated pharmacokinetic parameters. The objective of this study was to develop a population pharmacokinetic model for THC in occasional cannabis smokers. Twelve male volunteers (age: 20-28years, body weight: 62.5-91.0kg), tobacco (3-8 cigarette per day) and cannabis occasional smokers were recruited from the local community...
February 4, 2017: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/28135768/population-pharmacokinetics-analysis-of-intravenous-busulfan-in-chinese-patients-undergoing-hematopoietic-stem-cell-transplantation
#9
Xuemei Wu, Helin Xie, Weiwei Lin, Ting Yang, Nainong Li, Shanshan Lin, Xiaohong Yuan, Jinhua Ren, Xiaofan Li, Xian Huang
There are several reports describing population pharmacokinetic (popPK) models of busulfan (BU). However, limited information is available in Chinese hematopoietic stem-cell transplantation (HSCT) patients. The present study aimed to establish a popPK model of intravenous BU in Chinese HSCT patients for individualized drug therapy. The popPK model of BU was developed from a total of 284 concentration-time points from 53 patients. The effects of demographic and biochemical covariates were investigated by NONMEM(®) software...
January 30, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28125552/o-004-application-of-population-pharmacokinetic-modeling-to-develop-individualized-infliximab-dosing-strategies-in-pediatric-crohn-s-disease
#10
Adam Frymoyer, Daniel Hoekman, Tim de Meij, Thalia Hummel, Marc Benninga, Angelika Kindermann, Travis Piester, K T Park
BACKGROUND: Adequate infliximab (IFX) exposure is critical when treating Crohn's disease (CD), and trough concentrations <3 μg/mL are associated with loss of response. However, the pharmacokinetics of IFX are highly variable in children with CD, and this has made IFX dosing challenging in this population. Model-based drug dosing offers the potential for developing individualized dosing strategies. The objective of the current study was to evaluate the predictive performance and clinical utility of a previously published population pharmacokinetic model of IFX when applied to children with CD...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28099756/levofloxacin-effect-on-erlotinib-absorption-evaluation-of-the-interaction-in-undernutrition-situations-through-population-pharmacokinetic-analysis-in-rats
#11
Alejandro Pérez Pitarch, Beatriz Guglieri-López, Amparo Nacher, Virginia Merino, Matilde Merino-Sanjuan
The main objective of this study was to develop a pharmacokinetic model in order to describe the intestinal absorption of erlotinib in rat and to quantify the interaction of levofloxacin on this process in well- and undernourished rats. Absorption studies were performed in male Wistar rats. Concentration-time profiles in proximal and distal intestine were analysed through non-linear mixed effect modelling using the NONMEM software version 7.3. Simulations were performed in order to explore the influence of covariates on apparent absorption rate constant...
January 18, 2017: Biopharmaceutics & Drug Disposition
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
#12
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/28078682/population-pharmacokinetics-of-intravenous-clonidine-for-sedation-during-pediatric-extracorporeal-membrane-oxygenation-ecmo-and-continuous-veno-venous-hemofiltration-cvvh
#13
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/28078530/evaluation-of-the-population-pharmacokinetic-properties-of-lidocaine-and-its-metabolites-after-long-term-multiple-applications-of-a-lidocaine-plaster-in-post-herpetic-neuralgia-patients
#14
Roberta Bursi, Chiara Piana, Joachim Grevel, Dymphy Huntjens, Irmgard Boesl
BACKGROUND AND OBJECTIVES: Lidocaine 5% medicated plaster is the first lidocaine containing product for chronic use. As no previous investigations have been conducted to evaluate the population pharmacokinetics of long-term exposure to lidocaine 5% medicated plasters, further insights into the evaluation of the pharmacokinetic properties of lidocaine and its metabolites were needed for the assessment of its safety. METHODS: The population pharmacokinetic properties of lidocaine and its metabolites were evaluated after multiple applications of lidocaine 5% medicated plasters based on data collected for up to 14...
January 12, 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
#15
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/28063968/lack-of-genetic-association-between-oct1-abcb1-and-ugt2b7-variants-and-morphine-pharmacokinetics
#16
L M Nielsen, E Sverrisdóttir, T B Stage, S Feddersen, K Brøsen, L L Christrup, A M Drewes, A E Olesen
AIM: A high inter-individual variation in the pharmacokinetics and pharmacodynamics of morphine has been observed. Genetic polymorphisms in genes encoding the organic cation transporter isoform 1 (OCT1), the efflux transporter p-glycoprotein (ABCB1), and the UDP-glucuronosyltransferase-2B7 (UGT2B7) may influence morphine pharmacokinetics and thus, also pharmacodynamics. The aim of this study was to evaluate the association between OCT1, ABCB1, and UGT2B7 variants, and morphine pharmacokinetics and -dynamics in healthy volunteers...
March 1, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28052851/population-pharmacokinetic-model-of-doxycycline-plasma-concentrations-using-pooled-study-data
#17
Ashley M Hopkins, Jessica Wojciechowski, Ahmad Y Abuhelwa, Stuart Mudge, Richard N Upton, David J R Foster
The literature presently lacks a population pharmacokinetic analysis of doxycycline. This study aimed to develop a population pharmacokinetic model of doxycycline plasma concentrations that could be used to assess the power of bioequivalence between Doryx delayed-release tablets and Doryx MPC. Doxycycline pharmacokinetic data were available from eight phase 1 clinical trials following single/multiple doses of conventional-release doxycycline capsules, Doryx delayed-release tablets, and Doryx MPC under fed and fasted conditions...
March 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28050888/a-new-cyp3a5-3-and-cyp3a4-22-cluster-influencing-tacrolimus-target-concentrations-a-population-approach
#18
Franc Andreu, Helena Colom, Laure Elens, Teun van Gelder, Ronald H N van Schaik, Dennis A Hesselink, Oriol Bestard, Joan Torras, Josep M Cruzado, Josep M Grinyó, Nuria Lloberas
BACKGROUND: Single nucleotide polymorphisms (SNPs) in the CYP3A5 and CYP3A4 genes have been reported to be an important cause of variability in the pharmacokinetics of tacrolimus in renal transplant patients. The aim of this study was to merge all of the new genetic information available with tacrolimus pharmacokinetics to generate a more robust population model with data from renal transplant recipients. METHODS: Tacrolimus exposure data from 304 renal transplant recipients were collected throughout the first year after transplantation and were simultaneously analyzed with a population pharmacokinetic approach using NONMEM(®) version 7...
January 3, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28038962/confirming-model-predicted-pharmacokinetic-interactions-between-bedaquiline-and-lopinavir-ritonavir-or-nevirapine-in-patients-with-hiv-and-drug-resistant-tuberculosis
#19
Margreke J E Brill, Elin M Svensson, Mishal Pandie, Gary Maartens, Mats O Karlsson
Bedaquiline and its metabolite M2 are metabolised by CYP3A4. The antiretrovirals ritonavir-boosted lopinavir (LPV/r) and nevirapine inhibit and induce CYP3A4, respectively. Here we aimed to quantify nevirapine and LPV/r drug-drug interaction effects on bedaquiline and M2 in patients co-infected with HIV and multidrug-resistant tuberculosis (MDR-TB) using population pharmacokinetic (PK) analysis and compare these with model-based predictions from single-dose studies in subjects without TB. An observational PK study was performed in three groups of MDR-TB patients during bedaquiline maintenance dosing: HIV-seronegative patients (n = 17); and HIV-infected patients using antiretroviral therapy including nevirapine (n = 17) or LPV/r (n = 14)...
December 14, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28038961/determinants-of-gentamicin-concentrations-in-critically-ill-patients-a-population-pharmacokinetic-analysis
#20
Caspar J Hodiamont, Nicole P Juffermans, Catherine S C Bouman, Menno D de Jong, Ron A A Mathôt, Reinier M van Hest
When treating critically ill patients with gentamicin for severe infection, peak concentrations (Cmax) determine clinical efficacy and trough concentrations (Cmin) determine toxicity. Despite administration of body weight-standardised starting doses, a wide range of Cmax is generally observed. Furthermore, in therapeutic drug monitoring, several measures of renal function are used to predict appropriate Cmin and gentamicin dosing intervals, but the most accurate predictor is not known. This study aimed to quantify the impact of several patient parameters on gentamicin Cmax values and to determine which measure of renal function best predicts gentamicin clearance (CL)...
February 2017: International Journal of Antimicrobial Agents
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