PHARMACOKINETICS OF PROPOFOL AFTER A SINGLE-DOSE IN CHILDREN AGED 1-3YEARS WITH MINOR BURNS - COMPARISON OF 3 DATA-ANALYSIS APPROACHES

Background: No complete pharmacokinetic profile of propofol is yet ava ilable in children younger than 3 yr, whereas clinical studies have de monstrated that both induction and maintenance doses of propofol are i ncreased with respect to body weight in this age group compared to old er children and adults. This study was therefore undertaken to determi ne the pharmacokinetics of propofol after administration of a single d ose in aged children 1-3 yr requiring anesthesia for dressing change. Methods: This study was performed In 12 children admitted to the burn unit and in whom burn surface area was less than or equal to 12% of to tal body surface area. Exclusion criteria were: unstable hemodynamic c ondition, inappropriate fluid loading, associated pulmonary injury, or burn injury older than 2 days. Propofol (4 mg . kg(-1)) plus fentanyl (2.5 mu g . kg(-1)) was administered while the children were bathed an d the burn area cleaned during which the children breathed spontaneous ly a mixture of oxygen and nitrous oxide (50:50). Venous blood samples of 300 mu l were obtained at 5, 15, 30, 60, 90, and 120 min, and 3, 4 , 8, and 12 h after injection; an earlier sample was obtained from 8 o f 12 children. The blood concentration curves obtained for Individual children were analyzed by three different methods: noncompartmental an alysis, mixed-effects population model, and standard two-stage analysi s. Results: Using noncompartmental analysis, total clearance of propof ol (+/- SD) was 0.053 +/- 0.013 l . kg(-1). min(-1), volume of distrib ution at steady state 9.5 +/- 3.7 l . kg(-1), and mean residence time 188 +/- 85 min. Propofol pharmacokinetics were best described by a wei ght-proportional three-compartmental model In both population and two- stage analysis. Estimated and derived pharmacokinetic parameters were similar using these two pharmacokinetic approaches. Results of populat ion versus two-stage analysis are as follow: systemic clearance 0.049 versus 0,048 l . kg(-1). min(-1), volume of central compartment 1.03 v ersus 0.95 l . kg(-1), volume of distribution at steady state 8.09 ver sus 8.17 l . kg(-1). Conclusions: The volume of the central compartmen t and the systemic clearance were both greater than all values reporte d In older children and adults, This is consistent with the increased propofol requirements for both induction and maintenance of anesthesia in children aged 1-3 yr.