Correlation of the vancomycin 24-h area under the concentration-time curve (AUC24) and trough serum concentration in children with severe infection: A clinical pharmacokinetic study

2020 ◽  
Vol 92 ◽  
pp. 151-159 ◽  
Author(s):  
Satja Issaranggoon na Ayuthaya ◽  
Wasan Katip ◽  
Peninnah Oberdorfer ◽  
Aroonrut Lucksiri
Keyword(s):  
Serum Concentration ◽  
Clinical Pharmacokinetic ◽  
Pharmacokinetic Study ◽  
Severe Infection ◽  
Time Curve ◽  
Concentration Time ◽  
Trough Serum Concentration ◽  
Trough Serum

Optimizing Vancomycin Dosing through Pharmacodynamic Assessment Targeting Area under the Concentration-Time Curve/Minimum Inhibitory Concentration

2009 ◽  
Vol 44 (9) ◽  
pp. 751-765 ◽  
Author(s):  
C. Andrew Deryke ◽  
Donald P. Alexander
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Serum Concentration ◽  
Clinical Outcomes ◽  
Inhibitory Concentration ◽  
Health Care Systems ◽  
Time Curve ◽  
Concentration Time ◽  
Trough Serum Concentration ◽  
Trough Serum

Because of its activity against multidrug resistant gram-positive organisms, vancomycin is one of the antimicrobials most utilized in health care systems worldwide. Despite its widespread use, application of the pharmacodynamic principles governing vancomycin efficacy are not frequently considered in contemporary clinical practice. Although the vancomycin trough serum concentration has been used historically to assess the adequacy of a prescribed dose, data validating that this practice leads to improved patient outcomes do not exist. Alternatively, both in vitro and clinical outcomes data demonstrate improved results when an area under the concentration-time curve/minimum inhibitory concentration (AUC/MIC) of 400 mcg•h/mL or greater is achieved. This article describes the process through which individualized vancomycin dosing regimens targeting an AUC/MIC of 400 mcg•h/mL or greater, rather than trough serum concentration, at the beside can be derived. The equations, methodology, thought processes, benefits, potential pitfalls, and practical applicability of this method are specifically examined. Obtaining the actual MIC value—not an interpretation—from the microbiology laboratory and/or the MIC distribution for Staphylococcus aureus within one's own institution is essential for implementation of this method. Although vancomycin dosing recommendations suggested in contemporary practice guidelines are likely adequate for most patients, using the methods described here may lead to improved clinical outcomes for nonstandard conditions in patients who are critically ill and would benefit from an individualized dosing approach.

An initial dosing method for teicoplanin based on the area under the serum concentration time curve required for MRSA eradication

2011 ◽  
Vol 17 (2) ◽  
pp. 297-300 ◽  
Author(s):  
Naoko Kanazawa ◽  
Kazuaki Matsumoto ◽  
Tomohide Fukamizu ◽  
Akari Shigemi ◽  
Keiko Yaji ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Time Curve ◽  
Concentration Time ◽  
Dosing Method

scholarly journals Vancomycin Dosing in Healthy-Weight, Overweight, and Obese Pediatric Patients

2014 ◽  
Vol 19 (3) ◽  
pp. 182-188
Author(s):  
Lea S. Eiland ◽  
Kalyani B. Sonawane
Keyword(s):  
Serum Concentration ◽  
Pediatric Patients ◽  
Therapeutic Monitoring ◽  
Pharmacokinetic Parameters ◽  
Obese Patients ◽  
Healthy Weight ◽  
Serum Concentrations ◽  
Trough Serum Concentration ◽  
Trough Serum ◽  
Dosing Regimens

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics. METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L. RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment. CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.

scholarly journals PHARMACODYNAMICS EFFECT OF METHYLPREDNISOLONE TABLETS ON THE SERUM CONCENTRATION OF ANNEXIN A1: IN VIVO COMPARATIVE STUDY BETWEEN GENERIC AND INNOVATOR DRUG

2019 ◽  
Vol 12 (1) ◽  
pp. 414
Author(s):  
Hansen Nasif ◽  
Henny Lucida ◽  
Yanwirasti Yanwirasti ◽  
Yufri Aldi ◽  
Yori Yuliandra
Keyword(s):  
Serum Concentration ◽  
Peak Concentration ◽  
Peak Time ◽  
Annexin A1 ◽  
Onset Of Action ◽  
Time Curve ◽  
Concentration Time ◽  
Significant Difference ◽  
Generic Products

Objective: The aims of this study were to investigate the comparative pharmacodynamics effect of methylprednisolone (MP) innovator, MP branded generic, and MP generic products to the serum concentration of annexin A1 (AnxA1).Methods: It was conducted by two-way crossover design in male rabbits. AnxA1 was measured at 0, 0.5, 1, 2, 3, 5, 7, and 9 h after the administration of the drugs. The peak concentration (Cmax), the time at which the peak concentration was achieved (Tmax), and the area under the plasma concentration-time curve (AUC) were also determined.Results: The highest concentration and widest AUC of AnxA1 were obtained in MP innovator drug. MP innovator and branded generic reaches the peak time (Tmax) at the third 3rd h, while the MP generic reaches the peak time at the 5th h. The results showed that there was no significant difference in the serum concentration of AnxA1 between MP tablets after analyzed with a one-way analysis of variance.Conclusion: It could be concluded that the innovator drug of MP tablet gave the same effect on the serum concentration of AnxA1 than its generic counterparts, but an onset of action MP innovator and branded generic is faster than the generic product.

scholarly journals Carboplatin and Etoposide With or Without Palifosfamide in Untreated Extensive-Stage Small-Cell Lung Cancer: A Multicenter, Adaptive, Randomized Phase III Study (MATISSE)

2017 ◽  
Vol 35 (23) ◽  
pp. 2619-2623 ◽  
Author(s):  
Shadia I. Jalal ◽  
Philip Lavin ◽  
Gregory Lo ◽  
Francois Lebel ◽  
Lawrence Einhorn
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Serum Concentration ◽  
Small Cell ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Time Curve ◽  
Concentration Time ◽  
Phase Iii Study ◽  
Extensive Stage

Purpose To evaluate the efficacy of the addition of palifosfamide to carboplatin and etoposide in extensive stage (ES) small-cell lung cancer (SCLC). Patients and Methods MATISSE was a randomized, open-label, adaptive phase III study. Previously untreated patients with ES SCLC were randomly assigned in a 1:1 fashion to receive carboplatin at area under the serum concentration-time curve 5 on day 1 plus etoposide 100 mg/m2 per day on days 1 to 3 every 21 days (CE) or carboplatin at area under the serum concentration-time curve 4 on day 1 plus etoposide 100 mg/m2 per day plus palifosfamide 130 mg/m2 per day on days 1 to 3 every 21 days (PaCE). The primary end point was overall survival. Results In all, 188 patients were enrolled; 94 patients received CE and 94 patients received PaCE. The median age on both arms was 61 years. Six cycles of chemotherapy were completed on both arms of the study by approximately 50% of the patients. Serious adverse events were documented and did not differ significantly between patients receiving PaCE and those receiving CE. Median overall survival was similar between both arms with 10.03 months on PaCE and 10.37 months on CE ( P = .096). Conclusion The addition of palifosfamide to CE failed to improve survival in ES SCLC.

Determination of Clearance from a Trough Serum Concentration at Steady State

1987 ◽  
Vol 21 (1) ◽  
pp. 69-70
Author(s):  
Roy A. Pleasants ◽  
Ray R. Maddox ◽  
Richard E. Crass ◽  
Joseph M. DeVito
Keyword(s):  
Steady State ◽  
Serum Concentration ◽  
Trough Serum Concentration ◽  
Trough Serum

Safety, Pharmacokinetic, and Pharmacodynamic Phase I Dose-Escalation Trial of PF-00562271, an Inhibitor of Focal Adhesion Kinase, in Advanced Solid Tumors

2012 ◽  
Vol 30 (13) ◽  
pp. 1527-1533 ◽  
Author(s):  
Jeffrey R. Infante ◽  
D. Ross Camidge ◽  
Linda R. Mileshkin ◽  
Eric X. Chen ◽  
Rodney J. Hicks ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Focal Adhesion Kinase ◽  
Focal Adhesion ◽  
Dose Escalation ◽  
Group Performance ◽  
Geometric Mean ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Time Curve ◽  
Concentration Time

Purpose PF-00562271 is a novel inhibitor of focal adhesion kinase (FAK). The objectives of this study were to identify the recommended phase II dose (RP2D) and assess safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of PF-00562271. Patients and Methods Part 1 was a dose escalation without and with food. Part 2 enrolled specific tumor types in an expansion at the RP2D and also assessed the effect of PF-00562271 on single-dose midazolam PK in a subgroup of patients. Results Ninety-nine patients (median age, 60 years; 98% with Eastern Cooperative Oncology Group performance status of 0 or 1) were treated in 12 fasting and three fed cohorts. The 125-mg twice-per-day fed dose was deemed the maximum-tolerated dose (MTD) and RP2D. Grade 3 dose-limiting toxicities included headache, nausea/vomiting, dehydration, and edema. Nausea was the most frequently observed toxicity (60% of patients, all grades 1 or 2 at RP2D). PF-00562271 exposure increased with increasing dose; serum concentration–time profiles showed characteristic nonlinear disposition. Steady-state exposures were reached within 1 week. On coadministration, geometric mean values of midazolam maximal observed serum concentration and area under the serum concentration–time curve increased by 60% and more than two-fold, respectively. Of 14 patients evaluable by [18F]fluorodeoxyglucose positron emission tomography in the expansion cohorts, seven metabolic responses were observed. With conventional imaging, 31 patients had stable disease at first restaging scans, and 15 of these remained stable for six or more cycles. Conclusion The MTD and RP2D of PF-00562271 is 125 mg twice per day with food. PF-00562271 displayed time- and dose-dependent nonlinear PK and is likely a potent CYP 3A inhibitor. This first-in-class study supports further investigation of FAK as a promising therapeutic target.

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