title: Three monthly doses of palivizumab are not adequate for 5-month protection: a population pharmacokinetic analysis.
abstract: Recent guidelines in British Columbia, Canada have suggested that the use of a maximum of 3 monthly doses of palivizumab 15 mg/kg intramuscularly for RSV immunoprophylaxis of high risk infants born prior to the RSV season is adequate to provide protection against severe RSV disease for a 5-month RSV season. Efficacy was established, however, with 2 large, randomized controlled clinical studies using 5 monthly doses of immunoprophylaxis. To evaluate the differences in expected palivizumab exposures between the 2 dosing regimens (3 vs 5 monthly doses across a 5-month period), we used a population pharmacokinetic (PK) model that was developed using palivizumab PK data collected from 22 clinical studies with a total of 1800 subjects. This model adequately described observed palivizumab concentrations from the different pediatric studies and was subsequently used to simulate expected palivizumab serum concentrations for 3 monthly doses compared with 5 monthly doses in children younger than 24 months with chronic lung disease of prematurity and infants younger than 6 months postnatal age who were born at ≤ 35 weeks gestational age. Results from the population PK model indicated lower serum concentrations of palivizumab during the fourth and fifth months, after an abbreviated 3-monthly-dose regimen when compared with the mean trough concentrations seen with the 5-monthly-dose regimen studied in the pivotal clinical trials in premature infants. Specifically, during the fourth and fifth months, 52% and 85%, respectively, would have levels below the lowest concentration (fifth percentile) in those receiving the 5-monthly-dose regimen. Simulations using this model did not support a 3-monthly-dose regimen to protect against severe RSV disease during the typical 5-month season.
authors.affiliation: Medical and Scientific Affairs, MedImmune, LLC, Gaithersburg, MD, USA. Electronic address: laviaw@medimmune.com.
authors.forename: William V
authors.initials: WV
authors.lastname: La Via
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Notario
authors.forename: Xiang-Qing
authors.initials: XQ
authors.lastname: Yu
authors.forename: Shringi
authors.initials: S
authors.lastname: Sharma
authors.forename: Peter A
authors.initials: PA
authors.lastname: Noertersheuser
authors.forename: Gabriel J
authors.initials: GJ
authors.lastname: Robbie
mesh_terms: D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001955:British Columbia; D002986:Clinical Trials as Topic; D004334:Drug Administration Schedule; D006801:Humans; D007223:Infant; D007273:Injections, Intramuscular; D008954:Models, Biological; D000069455:Palivizumab; D017410:Practice Guidelines as Topic; D018357:Respiratory Syncytial Virus Infections / Q000517:prevention & control*; D012307:Risk Factors; D013997:Time Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000998:Antiviral Agents; D000069455:Palivizumab
keywords: Bronchopulmonary dysplasia (BPD); Chronic lung disease (CLD); Monoclonal antibody; Pediatric; Premature infant; Respiratory syncytial virus (RSV)