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dc.contributor.authorDowling, Thomas C.
dc.contributor.authorChavaillaz, Pierre A.
dc.contributor.authorYoung, David G.
dc.contributor.authorMelton-Celsa, Angela
dc.contributor.authorO'Brien, Alison
dc.contributor.authorThuninz- Roberson, Claire
dc.contributor.authorEdelman, Robert
dc.contributor.authorTacket, Carol O.
dc.identifier.citationDowling, T. C., Chavaillaz, P. A., Young, D. G., Melton-Celsa, A., O’Brien, A., Thuninz-Roberson, C., Edelman, R., & Tacket, C. O. (2005). Phase 1 Safety and Pharmacokinetic Study of Chimeric Murine-Human Monoclonal Antibody caStx2 Administered Intravenously to Healthy Adult Volunteers. Antimicrobial Agents and Chemotherapy, 49(5), 1808-1812, DOI: 10.1128/AAC.49.5.1808-1812.2005.en_US
dc.identifier.issn1098-6596 (online)
dc.identifier.issn0066-4804 (print)
dc.description.abstractHemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated cαStx2, that has neutralizing activity in a mouse model was produced and tested in healthy adult volunteers. In this phase I dose escalation study, cαStx2 was generally well tolerated. Pharmacokinetic studies indicated that clearance was stable over the dose range of 1.0 to 10 mg/kg of body weight (0.249 ± 0.023 ml/kg/h) but was higher for the 0.1-mg/kg dose (0.540 ± 0.078 ml/kg/h), suggesting saturable elimination. A similar nonlinear trend was observed for the volume of distribution, where average values ranged from 0.064 ± 0.015 liter/kg for the 1.0- to 10-mg/kg doses and 0.043 ± 0.005 for the 0.01-mg/kg dose. The relatively small volume of distribution suggests that the antibody is limited to the vascular (plasma) compartment. The mean half-life was 165 ± 66 h, with lowest values observed for the 0.1-mg/kg dose (56.2 ± 9.7 h) and the highest values reported for the 10.0-mg/kg dose (206.4 ± 12.4 h). Future studies are needed to confirm the safety of this cαStx2, and innovative clinical trials will be required to measure its efficacy in preventing or treating HUS.en_US
dc.subjectchimeric murine-human monoclonal antibodyen_US
dc.subject.meshHemolytic-Uremic Syndrome--prevention & controlen_US
dc.subject.meshShiga-Toxigenic Escherichia colien_US
dc.titlePhase 1 Safety and Pharmacokinetic Study of Chimeric Murine-Human Monoclonal Antibody caStx2 Administered Intravenously to Healthy Adult Volunteersen_US

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