Pharmacokinetic Parameters of Ciprofloxacin (500 mg/5 mL) Oral Suspension in Critically Ill Patients with Severe Bacterial Pneumonia: A Comparison of Two Dosages

2002 ◽  
Vol 14 (2) ◽  
pp. 175-180 ◽  
Author(s):  
R. Debon ◽  
D. Breilh ◽  
E. Boselli ◽  
M.C. Saux ◽  
F. Duflo ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Bacterial Pneumonia ◽  
Oral Suspension ◽  
Pharmacokinetic Parameters

Evaluation of Intravenous Phenobarbital Pharmacokinetics in Critically Ill Patients With Brain Injury

2022 ◽  
Author(s):  
Seyedeh Sana Khezrnia ◽  
Bita Shahrami ◽  
Mohammad Reza Rouini ◽  
Atabak Najafi ◽  
Hamid Reza Sharifnia ◽  
...  
Keyword(s):  
Brain Injury ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Normal Population ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Uv Detector ◽  
Therapeutic Goals ◽  
The Impact

Phenobarbital is still one of the drugs of choice in managing patients with brain injury in the intensive care unit (ICU). However, the impact of acute physiological changes on phenobarbital pharmacokinetic parameters is not well studied. This study aimed to evaluate the pharmacokinetic parameters of parenteral phenobarbital in critically ill patients with brain injury. Patients with severe traumatic or non-traumatic brain injury at high risk of seizure were included and followed for seven days. All patients initially received phenobarbital as a loading dose of 15 mg/kg over 30-minutes infusion, followed by 2 mg/kg/day divided into three doses. Blood samples were obtained on the first and fourth day of study at 1, 2, 5, 8, and 10 hours after the end of the infusion. Serum concentrations of phenobarbital were measured by high-pressure liquid chromatography (HPLC) with an ultraviolet (UV) detector. Pharmacokinetic parameters, including the volume of distribution (Vd), half-life (t1/2), and the drug clearance (CL), were provided by MonolixSuite 2019R1 software using stochastic approximation expectation-maximization (SAEM) algorithm and compared with previously reported parameters in healthy volunteers. Data from seventeen patients were analyzed. The mean value±standard deviation of pharmacokinetic parameters was calculated as follows: Vd: 0.81±0.15 L/kg; t1/2: 6.16±2.66 days; CL: 4.23±1.51 ml/kg/h. CL and Vd were significantly lower and higher than the normal population with the value of 5.6 ml/kg/h (P=0.002) and 0.7 L/kg (P=0.01), respectively. Pharmacokinetic behavior of phenobarbital may change significantly in critically ill brain-injured patients. This study affirms the value of early phenobarbital therapeutic drug monitoring (TDM) to achieve therapeutic goals.

scholarly journals Area under the Curve-Based Dosing of Vancomycin in Critically Ill Patients Using 6-Hour Urine Creatinine Clearance Measurement

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Bita Shahrami ◽  
Farhad Najmeddin ◽  
Saeideh Ghaffari ◽  
Atabak Najafi ◽  
Mohammad Reza Rouini ◽  
...  
Keyword(s):  
Renal Function ◽  
Creatinine Clearance ◽  
Critically Ill ◽  
Normal Renal Function ◽  
Critically Ill Patients ◽  
Area Under The Curve ◽  
Total Daily Dose ◽  
Pharmacokinetic Parameters ◽  
Concentration Data ◽  
Urine Creatinine

Background. The area under the curve- (AUC-) guided vancomycin dosing is the best strategy for individualized therapy in critical illnesses. Since AUC can be calculated directly using drug clearance (CLvan), any parameter estimating CLvan will be able to achieve the goal of 24-hour AUC (AUC24 h). The present study was aimed to determine CLvan based on 6-hour urine creatinine clearance measurement in critically ill patients with normal renal function. Method. 23 adult critically ill patients with an estimated glomerular filtration rate (eGFR) ≥60 mL/min who received vancomycin infusion were enrolled in this pilot study. Vancomycin pharmacokinetic parameters were determined for each patient using serum concentration data and a one-compartment model provided by MONOLIX software using stochastic approximation expectation-maximization (SAEM) algorithm. Correlation of CLvan with the measured creatinine clearance in 6-hour urine collection (CL6 h) and estimated creatinine clearance by the Cockcroft–Gault formula (CLCG) was investigated. Results. Data analysis revealed that CL6 h had a stronger correlation with CLvan rather than CLCG (r = 0.823 vs. 0.594; p < 0.001 vs. 0.003). The relationship between CLvan and CL6 h was utilized to develop the following equation for estimating CLvan: CLvan (mL/min) = ─137.4 + CL6 h (mL/min) + 2.5 IBW (kg) (R2 = 0.826, p < 0.001 ). Regarding the described model, the following equation can be used to calculate the empirical dose of vancomycin for achieving the therapeutic goals in critically ill patients without renal impairment: total daily dose of vancomycin (mg) = (─137.4CL6-h (mL/min) + 2.5 IBW (kg)) × 0.06 AUC24 h (mg.hr/L). Conclusion. For AUC estimation, CLvan can be obtained by collecting urine in a 6-hour period with good approximation in critically ill patients with normal renal function.

scholarly journals Effect of pharmacokinetic/pharmacodynamic ratio on tigecycline clinical response and toxicity in critically ill patients with multidrug-resistant Gram-negative infections

2020 ◽  
Vol 8 ◽  
pp. 205031212095889
Author(s):  
Jesus Ruiz ◽  
Paula Ramirez ◽  
Esther Villarreal ◽  
Mónica Gordon ◽  
María Ángeles Sánchez ◽  
...  
Keyword(s):  
Clinical Response ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Total Bilirubin Level ◽  
Optimal Dose ◽  
Multidrug Resistant ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Free Concentration ◽  
Gram Negative

Introduction: The information about the pharmacokinetics and optimal dose of tigecycline in critically ill patients with severe underlying diseases is limited and controversial. In this study, we evaluate the pharmacokinetic parameters of tigecycline in critically ill patients with multidrug-resistant Gram-negative infection and explore the association between the pharmacokinetic/pharmacodynamic ratio and treatment response. Methods: A prospective study was designed including critically ill patients treated with tigecycline for multidrug-resistant Gram-negative infections. Blood samples were collected at day 3–5 of treatment, and pharmacokinetics parameters were evaluated using NONMEM® software. Relationship between area under the free concentration–time curve and minimum inhibitory concentration ratio (fAUC/MIC) and treatment failure was evaluated. Association between tigecycline fAUC and hepatobiliary toxicity was also investigated. Results: Twenty-five critically ill patients were included in the study. In the pharmacokinetic model, weight and total bilirubin level were found to be significant predictors of tigecycline clearance. Fifteen (60.0%) patients achieved an fAUC/MIC ratio >4.5, seven (28.0%) an fAUC/MIC > 6.96 and only three (12.0%) an fAUC/MIC > 17.9. No differences in fAUC/MIC ratio were obtained between those patients with and without clinical failure (5.28 (IC95%: 2.57–7.94) vs 8.71 (3.57–13.84)). fAUC values were higher in those patients who suffered hepatobiliary disorders (7.63 (3.93–11.34) vs 17.63 (7.85–26.28) mg/L/h). Conclusion: An important percentage of critically ill patients with multidrug-resistant Gram-negative infection treated with tigecycline do not achieve an appropriate pharmacokinetic/pharmacodynamic value. Tigecycline fAUC seems to be associated with hepatobiliary disorders in this study population. The effect of fAUC/MIC ratio on clinical response remains unclear.

Usefulness of Semi-quantitative Procalcitonin Assay in Critically Ill Patients with Bacterial Pneumonia

2009 ◽  
Vol 41 (6) ◽  
pp. 342
Author(s):  
Seung Hwa Lee ◽  
Cheol-Hong Kim ◽  
Ji Youn Kim ◽  
Seon Wook Park ◽  
Young Wook Kim ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Bacterial Pneumonia

scholarly journals Pharmacokinetic Variability in Pediatrics and Intensive Care: Toward a Personalized Dosing Approach

2018 ◽  
Vol 21 ◽  
pp. 354-362 ◽  
Author(s):  
Amélie Marsot
Keyword(s):  
Drug Therapy ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Organ Support ◽  
Optimum Dose ◽  
Individual Factors ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Variability ◽  
Clinical Drug Development ◽  
Factors Influencing

Providing a safe and efficacious drug therapy for large and often heterogeneous populations is a challenging objective in clinical drug development and routine clinical practice. It has been known for years that the optimum dose required for many therapeutic agents among individuals is quite variable. A wide interindividual pharmacokinetic variability was described in clinically relevant populations such as pediatrics and critically ill patients. The aim of this article was to present the main individual factors influencing variability in these two populations and their applications. Growth and development are two specific features of children that are not observed in adults. And critically ill patients have a much higher level of sickness severity that is associated with profound pathophysiological changes. These particular features could lead to difficulties to attain therapeutic targets. Nonlinear mixed effects modeling is a common approach to identify unexplained population variability. This approach is often applied to evaluate and optimize drug therapy in particular populations. Numerous studies have been conducted in these two specific populations to characterize pharmacokinetic parameters and to identify individual factors influencing variability. Size, age and organ function appeared to be the main factors influencing pharmacokinetics in pediatrics. Factors influencing pharmacokinetics in critically ill patients were mainly cardiovascular system, organ dysfunction and organ support. Dosage individualization seems to be a key issue to optimize drug treatment in these specific populations. Clinically utility and safety of a model-based personalized drug therapy has been demonstrated for vancomycin in pediatrics. Many programs were available to optimize drug regimens, especially for antibiotic drugs in critically ill patients. This innovative personalized dosing approach is a promising way to optimize drug therapy in clinically relevant populations, such as pediatrics and critically ill patients.

scholarly journals Pharmacokinetic Assessment of Vancomycin Loading Dose in Critically Ill Patients

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Osvaldo Álvarez ◽  
Jose Cristian Plaza-Plaza ◽  
Manuel Ramirez ◽  
Alexis Peralta ◽  
Cristián A. Amador ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Serum Levels ◽  
The Body ◽  
Critically Ill Patient ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Loading Dose ◽  
Trough Serum ◽  
Number Of Patients

ABSTRACT The vancomycin loading dose (LD) of 25 to 30 mg/kg is a frequently practiced strategy to achieve effective concentrations from the first-treatment dose. However, considering only the body weight for dosing might be inadequate in critically ill patients due to pharmacokinetics changes. We sought to assess achieving optimal trough serum levels of vancomycin and AUC0–24/MIC in the first 24 h of treatment by using an LD based on population pharmacokinetic parameters of critically ill patients. We performed a concurrent cohort study over 22 months of patients with severe sepsis who received intravenous vancomycin. The patients were treated with three different strategies to initiate vancomycin: without an LD (group A), with an LD of 25 to 30 mg/kg (group B), and with an LD based on population pharmacokinetic parameters of the critically ill patient (group C). An optimal trough serum concentration was achieved in 5, 9, and 83% of patients in groups A, B, and C, respectively. The number of patients that reached optimal AUC0–24 was 2 of 18 (11%), 5 of 11 (46%), and 11 of 12 (92%) in groups A, B, and C, respectively. The statistical analysis for both parameters revealed significant differences in group C with respect to other groups. The administration of the LD calculated from population pharmacokinetic parameters from the beginning of therapy is a more efficient strategy to obtain adequate trough serum concentrations and AUC0–24/MIC in critical patients.

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