scholarly journals Population pharmacokinetic and pharmacodynamic analysis to support treatment optimization of combination chemotherapy with indisulam and carboplatin

2008 ◽  
Vol 66 (4) ◽  
pp. 485-497 ◽  
Author(s):  
Anthe S. Zandvliet ◽  
Jan H. M. Schellens ◽  
Christian Dittrich ◽  
Jantien Wanders ◽  
Jos H. Beijnen ◽  
...  
Keyword(s):  
Combination Chemotherapy ◽  
Population Pharmacokinetic ◽  
Treatment Optimization ◽  
Pharmacodynamic Analysis ◽  
Support Treatment

scholarly journals Impact of Maximizing Css/MIC Ratio on Efficacy of Continuous Infusion Meropenem Against Documented Gram-Negative Infections in Critically Ill Patients and Population Pharmacokinetic/Pharmacodynamic Analysis to Support Treatment Optimization

2021 ◽  
Vol 12 ◽  
Author(s):  
Pier Giorgio Cojutti ◽  
Milo Gatti ◽  
Matteo Rinaldi ◽  
Tommaso Tonetti ◽  
Cristiana Laici ◽  
...  
Keyword(s):  
Renal Function ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic ◽  
Treatment Optimization ◽  
Gram Negative ◽  
Cart Analysis ◽  
Pharmacodynamic Analysis ◽  
Favorable Clinical Outcome ◽  
Support Treatment

Introduction: optimal treatment of Gram-negative infections in critically ill patients is challenged by changing pathophysiological conditions, reduced antimicrobial susceptibility and limited therapeutic options. The aim of this study was to assess the impact of maximizing Css/MIC ratio on efficacy of continuous infusion (CI) meropenem in treating documented Gram-negative infections in critically ill patients and to perform a population pharmacokinetic/pharmacodynamic analysis to support treatment optimization.Materials and Methods: Classification and regression tree (CART) analysis was used to identify whether a cutoff of steady-state meropenem concentration (Css)-to-minimum inhibitory concentration (MIC) (Css/MIC) ratio correlated with favorable clinical outcome. A non-parametric approach with Pmetrics was used for pharmacokinetic analysis and covariate evaluation. The probability of target attainment (PTA) of the identified Css/MIC ratio was calculated by means of Monte Carlo simulations. Cumulative fraction of response (CFRs) were calculated against common Enterobacterales, P. aeruginosa and A. baumannii as well.Results: a total of 74 patients with 183 meropenem Css were included. CART analysis identified a Css/MIC ratio ≥4.63 as cutoff value significantly associated with favorable clinical outcomes. Multivariate regression analysis confirmed the association [OR (95%CI): 20.440 (2.063–202.522); p < 0.01]. Creatinine clearance (CLCR) was the only covariate associated with meropenem clearance. Monte Carlo simulations showed that, across different classes of renal function, dosages of meropenem ranging between 0.5 and 2 g q6h over 6 h (namely by CI) may grant PTAs of Css/MIC ratios ≥4.63 against susceptible pathogens with an MIC up to the EUCAST clinical breakpoint of 2 mg/L. The CFRs achievable with these dosages were very high (>90%) against Enterobacterales across all the classes of renal function and against P. aeruginosa among patients with CLCR < 30 ml/min/1.73 m2, and quite lower against A. baumannii.Discussion: our findings suggest that Css/MIC ratio ≥4.63 may be considered the pharmacodynamic target useful at maximizing the efficacy of CI meropenem in the treatment of Gram-negative infections in critically ill patients. Dosages ranging between 0.5 g q6h and 2 g q6h by CI may maximize the probability of favorable clinical outcome against meropenem-susceptible Gram-negative pathogens among critically ill patients having different degrees of renal function.

Population pharmacokinetic and pharmacodynamic analysis of tremelimumab in patients with metastatic melanoma

2014 ◽  
Vol 54 (10) ◽  
pp. 1108-1116 ◽  
Author(s):  
Erjian Wang ◽  
Dongwoo Kang ◽  
Kyun-Seop Bae ◽  
Margaret A. Marshall ◽  
Dmitri Pavlov ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Population Pharmacokinetic ◽  
Pharmacodynamic Analysis

scholarly journals Population Pharmacokinetic, Pharmacogenetic, and Pharmacodynamic Analysis of Cyclophosphamide in Ethiopian Breast Cancer Patients

2020 ◽  
Vol 11 ◽  
Author(s):  
Jemal Hussien Ahmed ◽  
Eyasu Makonnen ◽  
Ronald Kuteesa Bisaso ◽  
Jackson Kijumba Mukonzo ◽  
Alan Fotoohi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Population Pharmacokinetic ◽  
Breast Cancer Patients ◽  
Pharmacodynamic Analysis

scholarly journals Optimal Dosing of Ceftriaxone in Infants Based on a Developmental Population Pharmacokinetic-Pharmacodynamic Analysis

2020 ◽  
Vol 64 (11) ◽  
Author(s):  
Ya-Kun Wang ◽  
Yue-E Wu ◽  
Xue Li ◽  
Li-Yuan Tian ◽  
Muhammad Wasim Khan ◽  
...  
Keyword(s):  
Population Pharmacokinetics ◽  
Sampling Strategy ◽  
Optimal Dose ◽  
Community Acquired Pneumonia ◽  
Pharmacokinetic Analysis ◽  
Population Pharmacokinetic ◽  
Evidence Based ◽  
Open Label ◽  
Large Variability ◽  
Pharmacodynamic Analysis

ABSTRACT Ceftriaxone is a third-generation cephalosporin used to treat infants with community-acquired pneumonia. Currently, there is a large variability in the amount of ceftriaxone used for this purpose in this particular age group, and an evidence-based optimal dose is still unavailable. Therefore, we investigated the population pharmacokinetics of ceftriaxone in infants and performed a developmental pharmacokinetic-pharmacodynamic analysis to determine the optimal dose of ceftriaxone for the treatment of infants with community-acquired pneumonia. A prospective, open-label pharmacokinetic study of ceftriaxone was conducted in infants (between 1 month and 2 years of age), adopting an opportunistic sampling strategy to collect blood samples and applying high-performance liquid chromatography to quantify ceftriaxone concentrations. Developmental population pharmacokinetic-pharmacodynamic analysis was conducted using nonlinear mixed effects modeling (NONMEM) software. Sixty-six infants were included, and 169 samples were available for pharmacokinetic analysis. A one-compartment model with first-order elimination matched the data best. Covariate analysis elucidated that age and weight significantly affected ceftriaxone pharmacokinetics. According to the results of a Monte Carlo simulation, with a pharmacokinetic-pharmacodynamic target of a free drug concentration above the MIC during 70% of the dosing interval (70% fT>MIC), regimens of 20 mg/kg of body weight twice daily for infants under 1 year of age and 30 mg/kg twice daily for those older than 1 year of age were suggested. The population pharmacokinetics of ceftriaxone were established in infants, and evidence-based dosing regimens for community-acquired pneumonia were suggested based on developmental pharmacokinetics-pharmacodynamics.

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