Related Experiment Videos
Changes in vancomycin pharmacokinetics in critically ill infants
A G Gous1, M D Dance, J Lipman
1Department of Pharmacy, University of the Witwatersrand, Johannesburg, South Africa.
Insights
Critically ill infants receiving vancomycin show significant pharmacokinetic changes, particularly a larger initial volume of distribution (Vd). This highlights the need for therapeutic drug monitoring in this specific population.
Area of Science:
- Pharmacokinetics
- Critical Care Medicine
- Pediatric Pharmacology
Background:
- Vancomycin is crucial for treating serious infections in infants.
- Standard dosing regimens may not be optimal for critically ill infants due to altered physiology.
Purpose of the Study:
- To assess vancomycin pharmacokinetics in critically ill infants.
- To evaluate the efficacy of the standard recommended dose of 10 mg/kg every 6 hours.
Main Methods:
- Prospective study of infants in an Intensive Care Unit (ICU) receiving vancomycin.
- Serum vancomycin concentrations were measured on days 2 and 8 of therapy.
- Key pharmacokinetic parameters including volume of distribution (Vd), peak concentration (Cmax), and half-life (t1/2el) were determined.
Main Results:
- The mean vancomycin volume of distribution (Vd) was significantly larger on day 2 (0.81 L/kg) compared to day 8 (0.44 L/kg).
- This change in Vd led to significant alterations in mean Cmax and t1/2el over the treatment period.
- Aggressive fluid resuscitation in critically ill infants likely contributed to the large initial Vd and pharmacokinetic variability.
Conclusions:
- Critically ill infants exhibit significant pharmacokinetic variability, especially a large initial Vd.
- This variability suggests that routine therapeutic drug monitoring of vancomycin serum levels is indicated in this specific patient group.
- Individualized dosing adjustments may be necessary to ensure optimal vancomycin therapy in critically ill infants.
Abstract:
We aimed to assess the pharmacokinetics of vancomycin in critically ill infants, and to evaluate the standard recommended dose of 10 mg/kg 6 hourly. All infants admitted to the Baragwanath Hospital ICU who had arterial lines in situ, and for whom vancomycin 10 mg/kg 6 hourly was prescribed for an infective insult and who had parental consent, were included in the study. Vancomycin was infused over 60 minutes. Serum samples were taken immediately before the dose and at 30, 60, 120 and 300 minutes after the end of the vancomycin infusion, on days 2 and 8 of therapy. Extrapolated peak concentration (Cmax), trough concentration (Cmin), apparent volume of distribution (Vd), elimination half-life (t1/2el) and clearance (CL) were determined for each patient. Day 2 values were compared with those of day 8. Day 2 serum concentrations were assayed on 20 patients and day 8 concentrations in 15. The mean vancomycin Vd on day 2 (0.81 l/kg) was significantly (P = 0.007) larger than that on day 8 (0.44 l/kg). The change in Vd resulted in a significant change in mean Cmax (29.1 vs 35.5 micrograms/ml) (P = 0.02) and mean t1/2el (5.3 vs 3.4h) (P = 0.01) over the treatment period. Critically ill infants displayed a large initial volume of distribution which probably resulted from aggressive fluid resuscitation. This also results in a large variation in other pharmacokinetic parameters, namely Cmax and t1/2el. Although the routine monitoring of vancomycin serum concentrations remain controversial, we feel that in view of these large pharmacokinetic variations, the critically ill infant is a specific group where monitoring of vancomycin serum levels is indicated.