scholarly journals Optimal teicoplanin loading regimen to rapidly achieve target trough plasma concentration in critically ill patients

2019 ◽  
Vol 126 (3) ◽  
pp. 277-288 ◽  
Author(s):  
Hao Li ◽  
Lan Gao ◽  
Linjing Zhou ◽  
Yang Wang ◽  
Qi Li ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Trough Plasma Concentration ◽  
Trough Plasma

Association Between CYP3A4 Polymorphisms, Trough Imatinib Plasma Concentration and Cytogenetic Response in Chronic Phase Chronic Myeloid Leukemia (CML-CP)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3788-3788 ◽  
Author(s):  
Vikram Gota ◽  
Anupam Sharma ◽  
Amey Paradkar ◽  
Anand Patil ◽  
Navin Khattry ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Roc Curve ◽  
Chronic Phase ◽  
Cytogenetic Response ◽  
Molecular Response ◽  
Complete Cytogenetic Response ◽  
Trough Plasma Concentration ◽  
Pcr Rflp ◽  
Trough Levels ◽  
Trough Plasma

Abstract Abstract 3788 Introduction: Imatinib mesylate has demonstrated excellent efficacy as first-line therapy for treatment of chronic phase chronic myelogenous leukemia (CML-CP). The drug has a high inter-patient variability in pharmacokinetics (PK), and several factors are presumed to influence its PK. Imatinib is a substrate of CYP3A4 and CYP3A5 enzymes. However, the clinical significance of its metabolism on pharmacokinetics and therapeutic response is still unclear. Significantly higher in vivo CYP3A activity was reported recently in patients achieving complete molecular response than those who did not in a small cohort study. Several investigators in the past have tried to optimize imatinib dosing based on trough levels after the fourth treatment week. Picard S et al (Blood, 2007) showed that threshold plasma concentration of 1002 ng/ml on day 29 was associated with higher incidence of major molecular response. The primary objective of this study was to evaluate the association between CYP3A4 polymorphisms, trough plasma concentration of imatinib on day 8 and day 29 of treatment, and cytogenetic response. The secondary objective was to evaluate the potential of early (day 8) trough level monitoring to discriminate between responders and non-responders. Methods: All patients received standard 400 mg OD dose of imatinib. A single blood sample was collected on day 8 and day 29 prior to imatinib dosing for the determination of trough plasma concentration. Imatinib level was determined using High Performance Liquid Chromatography (HPLC). Cytogenetic response was assessed at 3 monthly intervals by Fluorescence In Situ Hybridization (FISH). Complete cytogenetic response (CCR) was defined as 0% of Philadelphia chromosome–positive cells in the bone marrow aspirate. Pharmacogenetic sample was collected from each patient at the beginning of the study to look for CYP3A4 polymorphism. Genotyping was carried out for *4 (rs55951658), *5 (rs55901263) and *18 (rs28371759) variants by PCR-RFLP technique. About 10% samples were chosen randomly for direct sequencing to confirm the PCR-RFLP findings. Median imatinib concentration in the CCR and non CCR groups was compared using non-parametric Mann-Whitney test. Receiver Operating Characteristic (ROC) curve analysis was performed to assess the discrimination potential of trough imatinib plasma levels for complete cytogenetic response (CCR). Results: Ninety eight patients were enrolled on this study, 70 males and 28 females. The median age was 33 years (Range 6 – 71 years). High interpatient variability in the trough concentration of imatinib was observed (Coefficient of variation = 64% and 56% for day 8 and day 29 respectively). However, none of the patients were found to have *4, *5 or *18 variant alleles. Genotype–PK or genotype-response association could not be evaluated as a result. Data on cytogenetic response at 12 months was available for 75 patients (60 CCR, 15 without CCR), 46 of whom also had trough imatinib levels measured on day 8 and day 29 (36 CCR, 10 without CCR). Median day 8 and day 29 trough concentrations were not significantly different in the group with CCR (1.71 and 1.91 μg/mL respectively) and the group without (1.31 and 1.64 μg/mL respectively). Regarding the discrimination potential of trough levels for CCR, day 8 concentrations failed to discriminate between responders and non-responders, whereas for the Day 29 levels, the area under the ROC curve (AUC) was 0.554, with best sensitivity (75%) and specificity (61%) at plasma threshold of 1.69 μg/mL. Conclusion: In this cohort of patients, common CYP3A4 variants did not contribute to the high inter-patient variability of imatinib levels. Early monitoring on Day 8 failed to discriminate responders from non-responders. Day 29 levels are a better predictor of complete cytogenetic response as shown in previous studies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk Factors for a Low Linezolid Trough Plasma Concentration in Acute Infections

2013 ◽  
Vol 57 (4) ◽  
pp. 1913-1917 ◽  
Author(s):  
Laura Morata ◽  
Marta Cuesta ◽  
Jhon F. Rojas ◽  
Sebastian Rodriguez ◽  
Merce Brunet ◽  
...  
Keyword(s):  
Risk Factors ◽  
Steady State ◽  
Plasma Concentration ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Content Type ◽  
Acute Infections ◽  
Trough Plasma Concentration ◽  
Dependent Activity ◽  
Trough Plasma

ABSTRACTLinezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (Cmin) and to determine factors associated with aCmin< 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with aCmindetermination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of lowCmin. A total of 29.5% of patients had aCmin< 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due toStaphylococcus aureus. The independent predictors ofCmin< 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037;P= 0.001) and infection due toS. aureus(OR, 5.906; 95% CI, 1.651 to 21.126;P= 0.006). A linezolidCminof <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due toS. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy.

A sensitive liquid chromatography-tandem mass spectrometry method for monitoring the caspofungin trough plasma concentration and its association with caspofungin efficacy in intensive-care-unit patients

RSC Advances ◽  
2015 ◽  
Vol 5 (127) ◽  
pp. 104806-104814 ◽  
Author(s):  
Qianting Yang ◽  
Taotao Wang ◽  
Jiao Xie ◽  
Lu Chen ◽  
Yan Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Intensive Care Unit ◽  
Intensive Care ◽  
Plasma Concentration ◽  
Tandem Mass ◽  
Spectrometry Method ◽  
Trough Plasma Concentration ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Trough Plasma

LC-MS/MS method for monitoring the caspofungin trough plasma concentration and its association efficacy in intensive-care-unit patients.

scholarly journals High-Trough Plasma Concentration of Afatinib Is Associated with Dose Reduction

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3425
Author(s):  
Takayuki Takahashi ◽  
Hideyuki Terazono ◽  
Takayuki Suetsugu ◽  
Hideki Sugawara ◽  
Junko Arima ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Adverse Effects ◽  
Dose Reduction ◽  
Roc Curve ◽  
High Performance ◽  
Kinase Inhibitor ◽  
Plasma Concentrations ◽  
Laboratory Data ◽  
Trough Plasma Concentration ◽  
Trough Plasma

Afatinib is used to treat non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation as a second-generation EGFR-tyrosine kinase inhibitor (TKI). Early prediction of adverse effects based on the pharmacokinetics of afatinib enables support for quality of life (QOL) in patients with no change in efficacy. We examined the pharmacokinetic relationship between trough plasma concentration and adverse effects and evaluated the utility of measuring the trough plasma concentration of afatinib as the first EGFR-TKI treatment for NSCLC in a prospective multicenter study. Twenty-four patients treated with afatinib were enrolled in this study. All blood samples were collected at the trough point, and plasma concentrations were measured using high-performance liquid chromatography–tandem mass spectrometry. Logistic regression analysis for the dose reduction of afatinib was performed, and the receiver operating characteristic (ROC) curve was plotted. Although all patients started afatinib at 40 mg/day, plasma concentrations were variable, and mean and median trough plasma concentrations were 32.9 ng/mL and 32.5 ng/mL in this study, respectively. Minimum and maximum trough plasma concentrations were 10.4 ng/mL and 72.7 ng/mL, respectively. This variability was speculated to involve personal parameters such as laboratory data. However, no patient characteristics or laboratory data examined correlated with the trough plasma concentration of afatinib, except albumin. Albumin showed a weak correlation with plasma concentration (r = 0.60, p = 0.009). The trough plasma concentration of afatinib was significantly associated with the dose reduction of afatinib (p = 0.047). The area under the ROC curve (AUC) for the trough plasma concentration of afatinib was 0.81. The cut-off value was 21.4 ng/mL. The sensitivity and specificity of the cut-off as a risk factor were 0.80 and 0.75. In summary, the trough plasma concentration of afatinib was associated with continued or reduced dosage because of the onset of several adverse effects, and a threshold was seen. Adverse effects not only lower QOL but also hinder continued treatment. Measuring plasma concentrations of afatinib appears valuable to predict adverse effects and continue effective therapy.

scholarly journals TRENDS IN PARATHYROID HORMONE PLASMA CONCENTRATION IN CRITICALLY ILL PATIENTS: PROSPECTIVE OBSERVATIONAL STUDY

2019 ◽  
Vol 72 (1) ◽  
pp. 40-46
Author(s):  
Aneta Czarnik ◽  
Tomasz Czarnik ◽  
Robert Kapłon ◽  
Marek Bolanowski
Keyword(s):  
Acute Kidney Injury ◽  
Parathyroid Hormone ◽  
Plasma Concentration ◽  
Renal Replacement Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Multiorgan Failure ◽  
Kidney Injury ◽  
Laboratory Reference ◽  
Concentration Levels

Introduction: There is no data in the literature regarding trends in parathormone serum concentration assessment in critically ill patients. The aim: To assess the parathyroid hormone plasma concentrations and kinetics in critically ill patients admitted to the intensive care unit due to multiorgan failure. Materials and methods: Thirty multiorgan failure (at least circulatory and respiratory failure) patients were included. Patients who met any of the following criteria were excluded: acute liver failure, end stage renal disease, hypercalcemia, parathyroid gland disease, severe vitamin D deficiency, admission from another ICU or readmission, age younger than 18 years, or lack of consent from relatives. We performed the parathyroid hormone plasma measurements in 12-hour time intervals. Results: The initial parathyroid hormone plasma concentration levels in the study group were rather variable and medians exceeded laboratory reference values. Especially in the acute kidney injury subpopulation treated with continuous renal replacement therapy these trends were emphasized. The initial parathyroid hormone plasma concentration levels in this group significantly exceeded laboratory reference values in 80% of patients. After initial spike we observed subsequent drop between second and third measurement. The distribution of plasma levels was rather variable between second and third measurement in this group of patients. Conclusions: The parathyroid hormone plasma concentration levels in the critically ill patients are variable. In the acute kidney injury subpopulation treated with continuous renal replacement therapy after initial significant spike we observed subsequent drop between second and third measurement.

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