Acetaminophen in cerebrospinal fluid in children

Background There are few studies describing acetaminophen (APAP) cerebrospinal fluid (CSF) concentrations in children. This current study was undertaken in children—from neonates to adolescents—in order to investigate age-related changes in the plasma to CSF equilibration half-time (Teq) of APAP.Methods Children (n=41) 1 week to 18 years of age undergoing (semi) elective surgery for placement or revision of a ventriculo-peritoneal shunt or insertion of a temporary external ventricular drain received a loading dose of 30–40 mg/kg APAP 1 h before scheduled surgery. Blood and CSF samples for APAP concentration analysis were collected during surgery. In those children with a temporary external drain, blood and CSF sampling were extended into the postoperative period. APAP and CSF pharmacokinetics were estimated using non-linear mixed-effects models. Size was standardized to a 70-kg person using allometric "1/4 power models".Results Median (25–75th percentile) age and weight of the patients included in this study were 12 months (3–62 months) and 10.0 kg (5.8–20.0 kg). Median (25–75th percentile) time between APAP loading dose administration and collection of blood samples and median time (25–75th percentile) between APAP loading dose and collection of CSF were, respectively, 125 min (95–210 min) and 133 min (33–202 min). The population mean Teq, standardized to a 70-kg person, was 1.93 h (CV 43%), an estimate similar to that described in adults (2.1 h). There was no relationship between age and Teq other than that predicted by size. APAP plasma concentrations ranged from 0.0 mg/l to 33.0 mg/l, APAP CSF concentrations ranged from 0.0 mg/l to 21.0 mg/l.Conclusion Size rather than blood–brain-barrier maturation determines Teq changes with age in children. We predict a neonate (3.5 kg), 1-year-old child (10 kg), 5-year-old child (20 kg), 10-year-old child (30 kg) and adult (70 kg) to have Teq values of 0.9, 1, 1.4, 1.6, and 1.93 h, respectively.