Plasma and cerebrospinal fluid concentrations of ibuprofen in pediatric patients and antipyretic effect: Pharmacokinetic-pharmacodynamic modeling analysis.

We aimed to determine the relationship between plasma and cerebrospinal fluid (CSF) concentrations of ibuprofen and the antipyretic effect in pediatric patients. A prospective cohort of infants and children aged 3 months to 15 years and treated with ibuprofen was studied. The patients received ibuprofen (via oral route, median dose of 10.0 mg/kg; 3.4-11.4 mg/kg range), samples of blood and CSF were collected, and body temperature was measured. Sequential analysis of the pharmacokinetic and pharmacodynamic data from 28 patients was performed using a population modeling approach. The observed concentration versus time data indicated substantial pharmacokinetic variability in absorption and distribution of ibuprofen between the patients. The pharmacokinetic modeling outcomes indicate that following a ∼25-minute lag time, ibuprofen is rapidly absorbed to the central compartment and rapidly equilibrates with the CSF, resulting in the total ibuprofen concentration in the CSF versus plasma (CCSF /Cplasma ) of 0.011 ± 0.007. The antipyretic effect of ibuprofen was best described by an indirect response PK-PD model incorporating patient baseline body temperature and ibuprofen concentration in the CSF. We conclude that the pharmacokinetic-pharmacodynamic modeling can be used to predict the time course of ibuprofen plasma and CSF concentrations and of the antipyretic effects in individual pediatric patients.

Measles-vaccinated Israeli boy with subacute sclerosing panencephalitis.

Subacute sclerosing panencephalitis is a rare neurologic disorder of childhood and adolescence. We describe a 16-year-old boy who manifested the disease despite proper vaccinations. He was hospitalized because of bedwetting, involuntary limb movements, abnormal speech, and balance disturbances. Immunoglobulin G antibodies against measles were strongly positive, with a high relative cerebrospinal fluid/serum ratio. Polymerase chain reaction for measles produced negative results. Electroencephalography registered slow activity with high voltage discharges every few seconds, and with triphasic complex morphology. Magnetic resonance imaging revealed diffuse white matter changes, mostly around the posterior regions and lateral ventricles. Treatment with valproic acid, levetiracetam, carbamazepine, and intravenous immunoglobulin G was ineffective. Inosiplex and interferon-ß-1a were also administrated. The patient became comatose, with generalized myoclonic jerks, and died 1 year later. An autopsy was not performed. This patient illustrates that subacute sclerosing panencephalitis should be suspected among young vaccinated subjects.