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https://www.readbyqxmd.com/read/28097633/meropenem-dosing-based-on-a-population-pharmacokinetic-pharmacodynamic-model-in-elderly-patients-with-infection-of-the-lower-respiratory-tract
#1
Qing-Tao Zhou, Bei He, Ning Shen, Ying Liang, Li-Na Sun
BACKGROUND: Meropenem is used for the treatment of severe lower respiratory tract infections (LRTIs) caused by multidrug-resistant Gram-negative bacilli. OBJECTIVE: We evaluated the clinical benefits of a strategy of meropenem dosing based on a population pharmacokinetics/pharmacodynamics (PK/PD) model in elderly patients with an LRTI. METHODS: In this prospective single-center open-label randomized controlled trial, 79 elderly patients with an LRTI caused by Gram-negative bacilli were randomized to a study group (SG) or a control group (CG)...
January 17, 2017: Drugs & Aging
https://www.readbyqxmd.com/read/28096164/pharmacodynamics-of-ceftaroline-plus-ampicillin-against-enterococcus-faecalis-in-an-in-vitro-pharmacokinetic-pharmacodynamic-model-of-simulated-endocardial-vegetations
#2
Brian J Werth, Laura M Shireman
The combination of ampicillin plus ceftaroline has been suggested to be more reliably synergistic against E. faecalis than ampicillin plus ceftriaxone using time-kill methods. The purpose of this study was to determine if this trend persists in a two-compartment-model of simulated endocardial vegetations(SEV) using clinically relevant pharmacokinetic exposures of these antimicrobials. Three clinically-derived E. faecalis strains were included in the study. The MICs of study antimicrobials were determined by broth microdilution...
January 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28090673/pharmacokinetic-pharmacodynamic-integration-and-modelling-of-oxytetracycline-for-the-porcine-pneumonia-pathogens-actinobacillus-pleuropneumoniae-and-pasteurella-multocida
#3
L Dorey, L Pelligand, Z Cheng, P Lees
Pharmacokinetic-pharmacodynamic (PK/PD) integration and modelling were used to predict dosage schedules of oxytetracycline for two pig pneumonia pathogens, Actinobacillus pleuropneumoniae and Pasteurella multocida. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined in broth and porcine serum. PK/PD integration established ratios of average concentration over 48 h (Cav0-48 h )/MIC of 5.87 and 0.27 μg/mL (P. multocida) and 0.70 and 0.85 μg/mL (A. pleuropneumoniae) for broth and serum MICs, respectively...
January 16, 2017: Journal of Veterinary Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28088839/pharmacokinetic-pharmacodynamic-modeling-of-the-pde4-inhibitor-tak-648-in-type-2-diabetes-early-translational-approaches-for-human-dose-prediction
#4
N Plock, S Vollert, M Mayer, G Hanauer, G Lahu
TAK-648 is a PDE4 inhibitor with demonstrated preclinical antidiabetic properties. Our objective was to develop a translational pharmacokinetic/pharmacodynamic (PK/PD) model for human type 2 diabetes (T2D) dose prediction using HbA1c results from a db/db mouse study. Estimated parameters in combination with tPDE4i values calculated for the clinical roflumilast dose of 500 μg were used to translate preclinical effects of TAK-648 to required exposure in humans. A first-in-human study with single TAK-648 doses of 0...
January 15, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28081545/mathematical-optimisation-of-the-cisplatin-plus-etoposide-combination-for-managing-extensive-stage-small-cell-lung-cancer-patients
#5
C Faivre, R El Cheikh, D Barbolosi, F Barlesi
BACKGROUND: Small-cell lung cancer (SCLC) represents one of the most aggressive forms of lung cancer. Despite the fair sensitivity of SCLC to chemotherapy and radiotherapy, the current standard treatment regimens have modest survival rates and are associated with potential life-threatening adverse events. Therefore, research into new optimised regimens that increase drug efficacy while respecting toxicity constraints is of primary importance. METHODS: A PK/PD model for the combination of cisplatin and etoposide to treat extensive-stage SCLC patients was generated...
January 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28074152/optimal-dosage-of-cefmetazole-for-intraoperative-antimicrobial-prophylaxis-in-patients-undergoing-surgery-for-colorectal-cancer
#6
Atsushi Tomizawa, Takatoshi Nakamura, Toshiaki Komatsu, Hiroshi Inano, Rumiko Kondo, Masahiko Watanabe, Koichiro Atsuda
BACKGROUND: Few studies have reported the dosage of cefmetazole (CMZ) for intraoperative antimicrobial prophylaxis in patients underwent surgery for colorectal cancer. We therefore examined the optimal intraoperative dosage of CMZ according to pharmacokinetic/pharmacodynamic (PK/PD) theory in patients who undergoing surgery for colorectal cancer. METHODS: The study group comprised 23 patients with colorectal cancer who underwent surgery, using CMZ as antimicrobial treatment to prevent postoperative infection...
2017: Journal of Pharmaceutical Health Care and Sciences
https://www.readbyqxmd.com/read/28069654/reduced-chance-of-hearing-loss-associated-with-therapeutic-drug-monitoring-of-aminoglycosides-in-the-treatment-of-multidrug-resistant-tuberculosis
#7
R van Altena, J A Dijkstra, M E van der Meer, J F Borjas Howard, J G W Kosterink, D van Soolingen, T S van der Werf, J W C Alffenaar
Hearing loss and nephrotoxicity are associated with prolonged treatment duration and higher dosage of amikacin and kanamycin. In our Tuberculosis Center, we have employed therapeutic drug monitoring (TDM) targeting pre-set pharmacokinetic/pharmacodynamic (PK/PD) surrogate endpoints in an attempt to maintain efficacy while preventing (oto-)toxicity. To evaluate this strategy, we retrospectively evaluated medical charts of TB patients treated with amikacin or kanamycin in the period 2000 - 2012.Patients with culture-confirmed multi- or extensively drug resistant tuberculosis (MDR/XDR-TB) receiving amikacin or kanamycin as part of their TB treatment for at least 3 days were eligible for inclusion in this retrospective study...
January 9, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28063154/pharmacological-indices-and-pulmonary-distribution-of-rifampicin-after-repeated-oral-administration-in-healthy-foals
#8
S Berlin, A Kirschbaum, L Spieckermann, S Oswald, M Keiser, M Grube, M Venner, W Siegmund
BACKGROUND: The treatment of equine lung infections by R. equi with rifampicin is empirically based because pharmacokinetic/pharmacodynamic (PK/PD) indices and pivotal clinical outcome data are not available. OBJECTIVES: Evaluation of pharmacokinetics and pulmonary distribution into epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALC) to predict antimicrobial activity in the lung using PK/PD-indices. STUDY DESIGN: Controlled, randomised, two-period, crossover, repeated-dose study with an initial arm to measure disposition after intravenous administration...
January 7, 2017: Equine Veterinary Journal
https://www.readbyqxmd.com/read/28063020/evaluation-of-amikacin-pharmacokinetics-and-pharmacodynamics-for-optimal-initial-dosing-regimen
#9
Hideo Kato, Mao Hagihara, Jun Hirai, Daisuke Sakanashi, Hiroyuki Suematsu, Naoya Nishiyama, Yusuke Koizumi, Yuka Yamagishi, Katsuhiko Matsuura, Hiroshige Mikamo
Amikacin has been one of the important antimicrobial agents against Gram-negative pathogens. However, there is discrepancy regarding the amikacin initial dosage, with some reports recently recommending ≥25 mg/kg and others the conventional dosage (15-20 mg/kg). Hence, we evaluated the optimal initial dosing regimen of amikacin. Pharmacokinetic (PK) parameters were estimated using a population PK analysis. The pharmacodynamic (PD) target was a ratio of ≥8 between the concentration achieved 1 h after beginning the infusion (C peak) and the minimal inhibitory concentration (MIC) of the liable bacteria...
January 6, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28035697/modeling-the-dose-response-relationship-the-fair-share-of-pharmacokinetic-and-pharmacodynamic-information
#10
M Gonzalez Sales, F Nekka, M Tanguay, P O Tremblay, J Li
AIM: To investigate the role of drug concentration samplings in the modelling of dose-response relationship. METHODS: Using an initial PK/PD model, a reference dataset was simulated. PK and PD samples were extracted to create reduced datasets. PK/PD and K-PD models were fitted to theses reduced datasets. Post hoc estimates from both types of models were compared to the initial PK/PD model and performance was assessed. RESULTS: K-PD models were largely biased when the drug has a non-linear elimination...
December 30, 2016: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28031207/pharmacokinetics-pharmacodynamics-of-pulmonary-delivery-of-colistin-against-pseudomonas-aeruginosa-in-a-mouse-lung-infection-model
#11
Yu-Wei Lin, Qi Tony Zhou, Soon-Ee Cheah, Jinxin Zhao, Ke Chen, Jiping Wang, Hak-Kim Chan, Jian Li
Colistin is often administered by inhalation and/or parenteral route for the treatment of respiratory infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa However, limited pharmacokinetic (PK) and pharmacodynamic (PD) data are available to guide the optimization of dosage regimens of inhaled colistin. In the present study, PK of colistin in epithelial lining fluid (ELF) and plasma was determined following intra-tracheal delivery of a single dose of colistin solution in neutropenic lung-infected mice...
December 28, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28017667/assessment-of-optimal-initial-dosing-regimen-with-vancomycin-pharmacokinetics-model-in-very-low-birth-weight-neonates
#12
Hideo Kato, Mao Hagihara, Naoya Nishiyama, Yusuke Koizumi, Hiroshige Mikamo, Katsuhiko Matsuura, Yuka Yamagishi
INTRODUCTION: Pharmacokinetic of vancomycin in very low birth weight neonates showed big variety, and limited data were available due to very minor population. These facts make it difficult to adjust its optimal initial dosage. Therefore, this study was to develop optimal dosing regimen of vancomycin in very low birth weight neonates. METHODS: Between 2010 and 2015, low birth weight neonates (≤1500 g) were included in a population pharmacokinetics analysis. Based on the pharmacokinetic parameters we estimated, we simulated individual blood concentrations of vancomycin and evaluated the probability of its pharmacokinetics/pharmacodynamics (PK/PD) target attainment, such as 24-h area under the concentration-time curve (AUC24)/MIC (≥400) and blood trough concentration (10-20 μg/mL), as primary measure for several dosing regimens by Monte Carlo simulation method...
December 22, 2016: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28013453/pk-pd-target-attainment-with-ceftolozane-tazobactam-using-monte-carlo-simulation-in-patients-with-various-degrees-of-renal-function-including-augmented-renal-clearance-and-end-stage-renal-disease
#13
Alan J Xiao, Luzelena Caro, Myra W Popejoy, Jennifer A Huntington, Ravina Kullar
INTRODUCTION: Ceftolozane/tazobactam is an antibacterial agent with potent in vitro activity against Gram-negative pathogens, including many extended-spectrum β-lactamase-producing Enterobacteriaceae and drug-resistant Pseudomonas aeruginosa. Because ceftolozane/tazobactam is primarily excreted renally, appropriate dose adjustments are needed for patients with renal impairment. Monte Carlo simulations were used to determine the probability of pharmacokinetic/pharmacodynamic target attainment for patients with varying degrees of renal function, including augmented renal clearance (ARC) and end-stage renal disease (ESRD) with hemodialysis...
December 24, 2016: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/28012683/might-real-time-pharmacokinetic-pharmacodynamic-optimisation-of-high-dose-continuous-infusion-meropenem-improve-clinical-cure-in-infections-caused-by-kpc-producing-klebsiella-pneumoniae
#14
Federico Pea, Paola Della Siega, Piergiorgio Cojutti, Assunta Sartor, Massimo Crapis, Claudio Scarparo, Matteo Bassetti
The effect of real-time pharmacokinetic/pharmacodynamic (PK/PD) optimisation of high-dose continuous-infusion meropenem on the clinical outcome of patients receiving combination antimicrobial therapy for treatment of KPC-producing Klebsiella pneumoniae (KPC-Kp) infections was retrospectively assessed. Data for all patients with KPC-Kp-related infections who received antimicrobial combination therapy containing high-dose continuous-infusion meropenem optimised by means of therapeutic drug monitoring (TDM) were retrieved...
December 8, 2016: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/28004376/population-pharmacokinetics-and-pharmacodynamics-modelling-of-dilmapimod-in-severe-trauma-subjects-at-risk-for-acute-respiratory-distress-syndrome
#15
Shuying Yang, Teodora Pene Dumitrescu
INTRODUCTION: Dilmapimod is a potent p38 mitogen-activated protein kinase (MAPK) inhibitor and was investigated in a study (NCT00996840) for its anti-inflammatory effect in non-head injury trauma patients at risk for developing acute respiratory distress syndrome (ARDS). The purpose of this paper is to present the details of the development of a population pharmacokinetic (PK) model, an empirical population placebo response model, and the exploration of a PK/pharmacodynamic (PD) model of dilmapimod...
December 21, 2016: Drugs in R&D
https://www.readbyqxmd.com/read/28001306/doxapram-mediated-increase-in-cardiac-output-reduces-opioid-plasma-concentrations-a-pk-pd-pk-pd-modeling-study-in-healthy-volunteers
#16
Margot Roozekrans, Erik Olofsen, Rutger van der Schrier, Merel Boom, René Mooren, Albert Dahan
Doxapram is an analeptic that induces ventilatory stimulation and increases blood pressure and cardiac output (CO). Its mechanism of action is blockade of background K(+) -channels expressed on type 1 carotid body cells. In the randomized controlled trial, the authors explored the role of the increase in CO by doxapram (plasma concentration (Cp) 1000-3,500 ng/mL) on the pharmacokinetics (PK) and pharmacodynamics of the potent opioid alfentanil (Cp 100-200 ng/mL). Population PK-PD analyses were performed on the doxapram PK-CO data and the alfentanil PK-antinociception data...
December 21, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27999883/the-pharmacokinetics-and-pharmacodynamics-of-alogliptin-in-children-adolescents-and-adults-with-type-2-diabetes-mellitus
#17
Caroline Dudkowski, Max Tsai, Jie Liu, Zhen Zhao, Eric Schmidt, Jeannie Xie
PURPOSE: The aim of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of a single 12.5- or 25-mg dose of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in pediatric (children and adolescents) and adult subjects with type 2 diabetes mellitus (T2DM). METHODS: A randomized, open-label, multicenter study was conducted in pediatric and adult subjects. Subjects in two pediatric groups (children and adolescents) were randomized 1:1 to receive a single oral dose of alogliptin 12...
December 20, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27999035/impact-of-vancomycin-protein-binding-on-target-attainment-in-critically-ill-children-back-to-the-drawing-board
#18
Pieter A J G De Cock, Sarah Desmet, Annick De Jaeger, Dominique Biarent, Evelyn Dhont, Ingrid Herck, Daphné Vens, Sofie Colman, Veronique Stove, Sabrina Commeyne, Johan Vande Walle, Peter De Paepe
OBJECTIVES: The objectives of this observational study were to investigate plasma protein binding and to evaluate target attainment rates of vancomycin therapy in critically ill children. PATIENTS AND METHODS: Paediatric ICU patients, in whom intravenous intermittent dosing (ID) or continuous dosing (CD) with vancomycin was indicated, were included. Covariates on unbound vancomycin fraction and concentration were tested using a linear mixed model analysis and attainment of currently used pharmacokinetic/pharmacodynamic (PK/PD) targets was evaluated...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27993147/erratum-to-artemether-lumefantrine-treatment-of-uncomplicated-plasmodium-falciparum-malaria-a-systematic-review-and-meta-analysis-of-day-7-lumefantrine-concentrations-and-therapeutic-response-using-individual-patient-data
#19
https://www.readbyqxmd.com/read/27978991/translational-pharmacokinetics-and-pharmacodynamics-of-monoclonal-antibodies
#20
REVIEW
Amrita V Kamath
Monoclonal antibodies (mAbs) are an important therapeutic class with complex pharmacology and interdependent pharmacokinetic (PK) and pharmacodynamics (PD) properties. Understanding the PK and PD of mAbs and their biological and mechanistic underpinnings are crucial in enabling their design and selection, designing appropriate efficacy and toxicity studies, translating PK/PD parameters to humans, and optimizing dose and regimen to maximize success in the clinic. Significant progress has been made in this field however many critical questions still remain...
September 2016: Drug Discovery Today. Technologies
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