Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome
The pharmacokinetics and safety ot 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, a...
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| Veröffentlicht in: | The Journal of pediatrics 1993-06, Vol.122 (6), p.974-981 |
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| container_title | The Journal of pediatrics |
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| creator | Romano, Michael J. Kearns, Gregory L. Kaplan, Sheldon L. Jacobs, Richard F. Killian, Anthony Bradley, John S. Moss, M. Michele Van Dyke, Russell Rodriguez, William Straube, Richard C. |
| description | The pharmacokinetics and safety ot 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 biexponentlal 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 (
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| doi_str_mv | 10.1016/S0022-3476(09)90031-2 |
| format | Article |
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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%.
Enterobacfer 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.</description><identifier>ISSN: 0022-3476</identifier><identifier>EISSN: 1097-6833</identifier><identifier>DOI: 10.1016/S0022-3476(09)90031-2</identifier><identifier>PMID: 8501580</identifier><identifier>CODEN: JOPDAB</identifier><language>eng</language><publisher>New York, NY: Mosby, Inc</publisher><subject>Adolescent ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - metabolism ; Bacterial Infections - therapy ; Biological and medical sciences ; Child ; Child, Preschool ; Female ; Humans ; Immunoglobulin M - administration & dosage ; Immunoglobulin M - adverse effects ; Immunoglobulin M - metabolism ; Immunomodulators ; Infant ; Male ; Medical sciences ; Pharmacology. Drug treatments ; Syndrome</subject><ispartof>The Journal of pediatrics, 1993-06, Vol.122 (6), p.974-981</ispartof><rights>1993 Mosby-Year Book, Inc. All right reserved</rights><rights>1993 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c389t-71fa39a6b92395b8d416ca496ce508505b5879c1b92ca30d58cfa0b54c99923</citedby><cites>FETCH-LOGICAL-c389t-71fa39a6b92395b8d416ca496ce508505b5879c1b92ca30d58cfa0b54c99923</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022347609900312$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4804741$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8501580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Romano, Michael J.</creatorcontrib><creatorcontrib>Kearns, Gregory L.</creatorcontrib><creatorcontrib>Kaplan, Sheldon L.</creatorcontrib><creatorcontrib>Jacobs, Richard F.</creatorcontrib><creatorcontrib>Killian, Anthony</creatorcontrib><creatorcontrib>Bradley, John S.</creatorcontrib><creatorcontrib>Moss, M. Michele</creatorcontrib><creatorcontrib>Van Dyke, Russell</creatorcontrib><creatorcontrib>Rodriguez, William</creatorcontrib><creatorcontrib>Straube, Richard C.</creatorcontrib><title>Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome</title><title>The Journal of pediatrics</title><addtitle>J Pediatr</addtitle><description>The pharmacokinetics and safety ot 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 biexponentlal 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%.
Enterobacfer 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.</description><subject>Adolescent</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - metabolism</subject><subject>Bacterial Infections - therapy</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Female</subject><subject>Humans</subject><subject>Immunoglobulin M - administration & dosage</subject><subject>Immunoglobulin M - adverse effects</subject><subject>Immunoglobulin M - metabolism</subject><subject>Immunomodulators</subject><subject>Infant</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Syndrome</subject><issn>0022-3476</issn><issn>1097-6833</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1993</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1u1DAUhS0EKtPCI1TyAiGQariexEm8QqOK0kpFLIa9dWM7HUNiB9sDmlfgqfH8aLasruTz3R-fQ8g1hw8cePNxDbBcsqpum3cg30uAirPlM7LgIFvWdFX1nCzOyEtymdIPAJA1wAW56ARw0cGC_F07_zRaZkKydN5gnFCHn87b7HSi6A1NONi8o2Gg9yvGVzcU6WY7oacPT18LkB0b3ewMW9Ep-KDH4HE8vPfB7G6o83S2xmGOTtMZs7M-J_rH5Q1Ndk4u0bTzJobJviIvBhyTfX2qV2R99_n77T17_Pbl4Xb1yHTVycxaPmAlsenlspKi70zNG421bLQVUP4letG1UvOia6zAiE4PCL2otZSl5Yq8PU6dY_i1tSmrySVtxxG9DdukWtG2QlRtAcUR1DGkFO2g5ugmjDvFQe0TUIcE1N5eBVIdElD7BdenBdt-subcdbK86G9OOiaN4xDRa5fOWN1B3da8YJ-OmC1W_HY2qqSLd7p4Ga3OygT3n0P-Af-5ots</recordid><startdate>19930601</startdate><enddate>19930601</enddate><creator>Romano, Michael J.</creator><creator>Kearns, Gregory L.</creator><creator>Kaplan, Sheldon L.</creator><creator>Jacobs, Richard F.</creator><creator>Killian, Anthony</creator><creator>Bradley, John S.</creator><creator>Moss, M. Michele</creator><creator>Van Dyke, Russell</creator><creator>Rodriguez, William</creator><creator>Straube, Richard C.</creator><general>Mosby, Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19930601</creationdate><title>Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome</title><author>Romano, Michael J. ; Kearns, Gregory L. ; Kaplan, Sheldon L. ; Jacobs, Richard F. ; Killian, Anthony ; Bradley, John S. ; Moss, M. Michele ; Van Dyke, Russell ; Rodriguez, William ; Straube, Richard C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-71fa39a6b92395b8d416ca496ce508505b5879c1b92ca30d58cfa0b54c99923</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1993</creationdate><topic>Adolescent</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - metabolism</topic><topic>Bacterial Infections - therapy</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Female</topic><topic>Humans</topic><topic>Immunoglobulin M - administration & dosage</topic><topic>Immunoglobulin M - adverse effects</topic><topic>Immunoglobulin M - metabolism</topic><topic>Immunomodulators</topic><topic>Infant</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Syndrome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Romano, Michael J.</creatorcontrib><creatorcontrib>Kearns, Gregory L.</creatorcontrib><creatorcontrib>Kaplan, Sheldon L.</creatorcontrib><creatorcontrib>Jacobs, Richard F.</creatorcontrib><creatorcontrib>Killian, Anthony</creatorcontrib><creatorcontrib>Bradley, John S.</creatorcontrib><creatorcontrib>Moss, M. Michele</creatorcontrib><creatorcontrib>Van Dyke, Russell</creatorcontrib><creatorcontrib>Rodriguez, William</creatorcontrib><creatorcontrib>Straube, Richard C.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of pediatrics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Romano, Michael J.</au><au>Kearns, Gregory L.</au><au>Kaplan, Sheldon L.</au><au>Jacobs, Richard F.</au><au>Killian, Anthony</au><au>Bradley, John S.</au><au>Moss, M. Michele</au><au>Van Dyke, Russell</au><au>Rodriguez, William</au><au>Straube, Richard C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome</atitle><jtitle>The Journal of pediatrics</jtitle><addtitle>J Pediatr</addtitle><date>1993-06-01</date><risdate>1993</risdate><volume>122</volume><issue>6</issue><spage>974</spage><epage>981</epage><pages>974-981</pages><issn>0022-3476</issn><eissn>1097-6833</eissn><coden>JOPDAB</coden><abstract>The pharmacokinetics and safety ot 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 biexponentlal 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%.
Enterobacfer 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.</abstract><cop>New York, NY</cop><pub>Mosby, Inc</pub><pmid>8501580</pmid><doi>10.1016/S0022-3476(09)90031-2</doi><tpages>8</tpages></addata></record> |
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| ispartof | The Journal of pediatrics, 1993-06, Vol.122 (6), p.974-981 |
| issn | 0022-3476 1097-6833 |
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| subjects | Adolescent Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - metabolism Bacterial Infections - therapy Biological and medical sciences Child Child, Preschool Female Humans Immunoglobulin M - administration & dosage Immunoglobulin M - adverse effects Immunoglobulin M - metabolism Immunomodulators Infant Male Medical sciences Pharmacology. Drug treatments Syndrome |
| title | Single-dose pharmacokinetics and safety of HA-1A, a human IgM anti-lipid-A monoclonal antibody, in pediatric patients with sepsis syndrome |
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