Maturational pharmacokinetics of single intravenous bolus of propofol

Summary Background:  Our aim was to document propofol pharmacokinetics in preterm and term neonates following a single intravenous bolus and compare these estimates with pharmacokinetics findings in toddlers and young children. Methods:  Newly collected observations following intravenous bolus administration of propofol in preterm and term neonates ( n  =   9) were compared with earlier reported pharmacokinetic estimates in toddlers and young children. Data are reported by median and range. Mann–Whitney U‐ test or correlation was used to analyze differences in pharmacokinetic findings between neonates, toddlers and young children. Results:  Concentration‐time profiles obtained were interpreted by two‐stage analysis as a three compartment open model in nine neonates with a median weight of 2.51 (range 0.91–3.8) kg and a median postmenstrual age (PMA) of 36 (range 27–43) weeks. Median clearance (CL) was 13.6 (range 3.7–78.2) ml·min −1 ·kg −1 and median apparent volume of distribution at steady state ( V ss ) was 3.7 (1.33–7.96) l·kg −1 . Following allometric scaling and standardization to 70 kg, median CL was 442 (range 97–2184) ml·min −1 ·70 kg −1 . Compared with earlier reported observations in toddlers and children, median clearance (kg·min −1 ) was significantly lower in neonates ( P  <   0.01) and these differences remained significant after allometric scaling (70 kg·min −1 ) while V ss (l·kg −1 ) was significantly lower in neonates ( P  <   0.01). Conclusions:  Propofol disposition is significantly different in neonates compared with toddlers and young children, reflecting both ontogeny and differences in body composition. Based on the reduced clearance of propofol, a longer recovery time is more likely to occur in neonates.