Linked Life Data

14691437

Source:http://linkedlifedata.com/resource/pubmed/id/14691437

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-23
pubmed:abstractText
BACKGROUND: Increase in vascular permeability and multiorgan dysfunction after cardiopulmonary bypass (CPB) are barriers to successful cardiac surgery in infants. Complement inhibition with TP10, a C3/C5 convertase inhibitor (AVANT Immunotherapeutics, Needham, Mass), blunts post-CPB organ dysfunction in the neonatal pig. Methods and results The pharmacokinetics and safety of TP10 in infants (age <1 year, n = 15) undergoing CPB were examined in a phase I/II open-label prospective trial. TP10 (10 mg/kg) was given intravenously before CPB and also added (10 mg/100 mL prime volume) to the CPB circuit. TP10 plasma levels correlated with C3a levels and measures of clinical course. All infants survived. No adverse events were attributed to TP10. TP10 plasma concentration fell to < or =60 microg/mL 12 hours after CPB. A 2-compartment model was fit to the TP10 blood levels as a function of time. Based on this model, an initial dose of 10 mg/kg over 0.5 hours followed by 10 mg/kg over 23.5 hours is the most appropriate for maintaining TP10 concentration between 100 microg/mL and 160 microg/mL for 24 hours after CPB. C3a was lower 12 hours after CPB than before CPB and still lower 24 hours after CPB. TP10 concentration was inversely correlated with the 12-hour post-CPB to pre-CPB ratio of C3a (Spearman rho -0.76, P = -.016), and with total (rho -0.56, P =.047) and net (rho -0.85, P =.0016) fluid and blood product administration/kg >24 hours after CPB. CONCLUSIONS: TP10 administration to infants appears safe. Pharmacokinetic analysis generated an optimal dosing strategy to achieve effective TP10 levels for 24 hours after CPB. In the infant, TP10 appears to decrease CPB-induced complement activation and protect vascular function. These results support a phase III trial of TP10 in infants requiring CPB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1097-6744
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
147
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
173-80
pubmed:dateRevised
2009-11-3
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Pharmacokinetics and safety of TP10, soluble complement receptor 1, in infants undergoing cardiopulmonary bypass.
pubmed:affiliation
Department of Pediatrics, Division of Cardiology, Duke University Medical Center, Durham, NC 27710, USA. li000001@mc.duke.edu
pubmed:publicationType
Journal Article, Clinical Trial, Multicenter Study, Clinical Trial, Phase II, Clinical Trial, Phase I