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Population pharmacokinetics of raxibacumab in healthy adult subjects.

Oosterholt, SP; Della Pasqua, O; (2021) Population pharmacokinetics of raxibacumab in healthy adult subjects. British Journal of Clinical Pharmacology 10.1111/bcp.14894. (In press).

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Abstract

AIM: Raxibacumab is a fully humanized monoclonal antibody that blocks the interaction of Bacillus anthracis toxins, thereby protecting target cells from its effects. Raxibacumab is approved in the USA for the treatment of adults and children with inhalational anthrax in combination with antibiotics, and for prophylaxis of inhalational anthrax. The aim of this investigation was to characterise the population pharmacokinetics and assess the effect of baseline demographic covariates on the disposition of raxibacumab. METHODS: The data used for this analysis were obtained from 3 clinical trials and include 2229 blood samples from 322 healthy subjects who were randomized to receive a 40 mg/kg intravenous dose of raxibacumab over a period of 2.25 hours. Population pharmacokinetic modelling was performed using a nonlinear mixed effects approach. Secondary parameters of interest were the area under the curve, maximum concentration and the time of serum raxibacumab concentrations greater than or equimolar to the highest serum protective antigen concentrations observed for at least 28 days in any monkey challenged with B. anthracis that died. RESULT: Raxibacumab exposure in healthy subjects was described by a 2-compartment model. Inter-individual variability (IIV) was estimated for all model parameters, whilst residual variability was described by a proportional and additive error model. Weight was the only influential covariate with significant effect on disposition parameters. CONCLUSION: A dose of 40 mg/kg provided comparable exposure across the overall healthy subject population. IIV in raxibacumab versus time profiles could partially be accounted for by differences in body weight.

Type: Article
Title: Population pharmacokinetics of raxibacumab in healthy adult subjects.
Location: England
DOI: 10.1111/bcp.14894
Publisher version: https://doi.org/10.1111/bcp.14894
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Phase I, anthrax, antibodies, population pharmacokinetics, raxibacumab
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/10127806
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