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: Michael R Pranzatelli, Elizabeth D Tate, Steven J Verhulst, Salvatore J Bertolone, Deepika Bhatla, Meaghan Granger, Joseph Lebowizc, Sharon K Lockhart, Joseph M Wiley
• Journal: Journal of pediatric hematology/oncology (J Pediatr Hematol Oncol) Vol. 32 Issue 5 Pg. e167-72 (Jul 2010) ISSN: 1536-3678 [Electronic] United States
• PMID: 20606544 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents
• Immunoglobulin M
• Immunoglobulins, Intravenous
• Rituximab
• Adrenocorticotropic Hormone

Topics

• Adolescent
• Adrenocorticotropic Hormone (administration & dosage)
• Antibodies, Monoclonal (administration & dosage, pharmacokinetics)
• Antibodies, Monoclonal, Murine-Derived
• Antineoplastic Agents (blood, pharmacokinetics)
• Child
• Child, Preschool
• Clinical Trials, Phase I as Topic
• Clinical Trials, Phase II as Topic
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Immunoglobulin M (blood)
• Immunoglobulins, Intravenous (administration & dosage)
• Immunotherapy
• Infant
• Male
• Opsoclonus-Myoclonus Syndrome (immunology, metabolism)
• Prospective Studies
• Rituximab
• Treatment Outcome