Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome.
Publication/Presentation Date
6-1-1993
Abstract
The pharmacokinetics and safety of HA-1A (Nebacumab), a human IgM monoclonal antibody with specificity for the lipid A region of endotoxin, were evaluated in a multicenter trial of pediatric patients with sepsis syndrome or septic shock. Forty-two patients received a total of 44 infusions of drug, at a dose of 3 mg/kg (maximum 100 mg). The mean age was 7 years 10 months (range, 11 months to 16 years 7 months). The pharmacokinetic behavior of HA-1A during 36 hours was best described by a one-compartment open model. Clearance (6.1 +/- 2.0 ml/kg per hour) and apparent volume of distribution at steady state (0.11 +/- 0.03 L/kg) were larger than values reported previously in adults with sepsis syndrome. Elimination half-life (14.5 +/- 6.8 hours) and plasma concentration after infusion (30.7 +/- 14.5 mg/L) were similar to adults' values. In an additional three patients studied for 72 hours after administration, a biexponential function (i.e., two-compartment open model) best described the pharmacokinetic behavior of HA-1A: clearance (1.5 +/- 1.4 ml/hr per kilogram) and apparent volume of distribution at steady state (0.2 +/- 0.02 L/kg) were different (p < 0.002) from values observed in children's blood samples during 36 hours. Within the pediatric population, no age-related differences in pharmacokinetics could be detected. Drug disposition was unaffected by renal or hepatic dysfunction. Decreased blood pressure was the most frequently reported adverse event; 4 (9%) episodes in 44 infusions were considered possibly related to the study drug. Gram-negative bacteremia was documented in 23 (55%) of 42 patients. The overall mortality rate was 31%. Enterobacter cloacae was the most common pathogen isolated. Haemophilus influenzae type b was isolated from one child with sepsis syndrome. We conclude that infusion of HA-1A in children is associated with a low incidence of side effects. The pharmacokinetic-pharmacodynamic behavior of HA-1A in children requires further study to determine whether developmental differences exist and how these differences might affect drug administration. Efficacy remains to be studied.
Volume
122
Issue
6
First Page
974
Last Page
981
ISSN
0022-3476
Published In/Presented At
Romano, M. J., Kearns, G. L., Kaplan, S. L., Jacobs, R. F., Killian, A., Bradley, J. S., Moss, M. M., Van Dyke, R., Rodriguez, W., & Straube, R. C. (1993). Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome. The Journal of pediatrics, 122(6), 974–981. https://doi.org/10.1016/s0022-3476(09)90031-2
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
8501580
Department(s)
Department of Pediatrics
Document Type
Article