title: Pediatric dosing of rituximab revisited: serum concentrations in opsoclonus-myoclonus syndrome.
abstract: To longitudinally assess serum concentrations of rituximab, it was administered intravenously to 25 children with opsoclonus-myoclonus syndrome at 375 mg/m2 on each of 4 consecutive weeks with (Group I and II) or without (Group III) conventional immunotherapy. Serum rituximab levels, drawn before and after each infusion and at later intervals, were analyzed by enzyme-linked immunosorbent assay. Rituximab concentration increased stepwise with each infusion, dropping by the next infusion, thereby forming 4 discrete peaks (Cmax) and troughs (Cmin). It then fell precipitously to trace levels at 4 months. However, Cmax and Cmin curves differed significantly between groups. Compared with the youngest children (Group I), the oldest (Group III) had a 34% lower rituximab concentration at the fourth infusion, 45% less IgM depletion 1 month later, and received 20% less rituximab when the dose was recalculated as mg/kg. Serum IgM and rituximab levels were negatively correlated. Peak rituximab concentration did not correlate with adrenocorticotropic hormone dose. These results indicate that the degree of serum IgM depletion is a useful indicator for rituximab dose equivalency in children of different ages. They also suggest that pediatric rituximab dosing should be based on body weight, not surface area. (ClinicalTrials.gov NCT00244361).
authors.affiliation: National Pediatric Myoclonus Center, Southern Illinois University School of Medicine, Springfield, IL, USA. mpranzatelli@siumed.edu
authors.forename: Michael R
authors.initials: MR
authors.lastname: Pranzatelli
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Tate
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Verhulst
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Bertolone
authors.forename: Deepika
authors.initials: D
authors.lastname: Bhatla
authors.forename: Meaghan
authors.initials: M
authors.lastname: Granger
authors.forename: Joseph
authors.initials: J
authors.lastname: Lebowizc
authors.forename: Sharon K
authors.initials: SK
authors.lastname: Lockhart
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Wiley
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage; D007167:Immunotherapy; D007223:Infant; D008297:Male; D053578:Opsoclonus-Myoclonus Syndrome / Q000276:immunology / Q000378:metabolism*; D011446:Prospective Studies; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D007075:Immunoglobulin M; D016756:Immunoglobulins, Intravenous; D000069283:Rituximab; D000324:Adrenocorticotropic Hormone