Three monthly doses of palivizumab are not adequate for 5-month protection: a population pharmacokinetic analysis.

Autor: La Via WV; Medical and Scientific Affairs, MedImmune, LLC, Gaithersburg, MD, USA. Electronic address: laviaw@medimmune.com., Notario GF, Yu XQ, Sharma S, Noertersheuser PA, Robbie GJ
Jazyk: angličtina
Zdroj: Pulmonary pharmacology & therapeutics [Pulm Pharmacol Ther] 2013 Dec; Vol. 26 (6), pp. 666-71. Date of Electronic Publication: 2013 Mar 19.
DOI: 10.1016/j.pupt.2013.03.007
Abstrakt: 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.
(Copyright © 2013 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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