BACKGROUND: Delayed achievement of target vancomycin serum concentrations may adversely affect clinical outcomes. The objective of this retrospective study was to compare the prediction accuracy of different body weight descriptors for volume of distribution and to propose an optimal loading dose (LD) for continuous infusion regimens in adults. METHODS: Pharmacokinetic variables were computed using one-compartmental analysis. Simulated LDs of vancomycin were evaluated for each patient. RESULTS: Volume of distribution, clearance, and half-life median values (interquartile range) for vancomycin in the study population (n = 30) were 0.45 (0.39-0.61) L.kg-1, 0.026 (0.015-0.040) L.h-1.kg-1, and 10.3 (7.7-21.3) h, respectively. The observed volume of distribution was better predicted by total body weight (TBW) than by the ideal body weight or the adjusted body weight. CONCLUSIONS: An LD of 10.7 mg per kg TBW was optimal in our study population. Using this LD, 17.9% of simulated vancomycin serum levels were just below the therapeutic range, only 10.7% concentrations exceeded the target range and no concentration was toxic. The use of a LD would lead to reduced median time to reach target concentrations from 17 to 1 h.

• Klíčová slova
• Vancomycin, body weight, continuous infusion, obesity, pharmacokinetics, volume of distribution,
• MeSH
• intravenózní infuze MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita MeSH
• péče o pacienty v kritickém stavu metody   MeSH
• počítačová simulace MeSH
• poločas MeSH
• retrospektivní studie MeSH
• senioři MeSH
• tělesná hmotnost MeSH
• vankomycin aplikace a dávkování   krev   terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• vankomycin MeSH

PURPOSE: Delayed achievement of target vancomycin serum concentrations may adversely affect clinical outcomes. The objective of this retrospective study was to explore the real frequency of loading dose use and to evaluate the impact of loading dose for the achievement of vancomycin PK/PD target in adult patients treated with intermittent vancomycin. As a secondary aim we determined optimal vancomycin loading dose based on individual pharmacokinetic calculations. METHODS: Vancomycin pharmacokinetic models were computed using two-compartmental analysis. Based on these models AUC24 were calculated. Unpaired t-test was used to compare AUC24 achieved in patients treated with and without vancomycin loading dose. RESULTS: Vancomycin loading dose was administered only in 17.8% patients. Volume of distribution and clearance median values (interquartile range) for vancomycin in whole study population (n = 45) were 0.69 (0.55-0.87) L/kg and 0.0304 (0.0217-0.0501) L/h/kg, respectively. The AUC24 was significantly higher in patients taking loading dose compared with the group without loading dose: mean (SD) AUC24 was 496 (101) vs. 341 (77) mg h/L. Proportion of patients reaching PK/PD goal was 87.5% and 24.3% with and without loading dose administration, respectively. Considering individual pharmacokinetic parameters optimal vancomycin loading dose was 27.5 mg/kg of body weight. CONCLUSIONS: Loading dose administration plays crucial part in rapid attainment of vancomycin PK/PD target in adult patient treated with intermittent vancomycin, although it is not frequently used in clinical practise. The optimal loading dose of 25-30 mg/kg of body weight should be routinely administered to adult patients treated with intermittent vancomycin.

• Klíčová slova
• Intermittent infusion, Loading dose, Pharmacokinetics, Therapeutic drug monitoring, Vancomycin,
• MeSH
• antibakteriální látky aplikace a dávkování   krev   farmakokinetika   farmakologie   MeSH
• infuzní pumpy MeSH
• kreatinin krev   MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• plocha pod křivkou MeSH
• počítačová simulace MeSH
• retrospektivní studie MeSH
• senioři MeSH
• vankomycin aplikace a dávkování   krev   farmakokinetika   farmakologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• kreatinin MeSH
• vankomycin MeSH