tetano
Editor, Senior Moderator
Drug Test Anal
. 2021 Jul 2.
doi: 10.1002/dta.3122. Online ahead of print.
Pharmacokinetic profiles of a SARS-COV-2 neutralizing antibody BD-604 in cynomolgus monkeys
Feng Gao[SUP] 1 [/SUP], Xu Zhang[SUP] 1 [/SUP]
Affiliations
Abstract
Background: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has spread worldwide as a severe pandemic and effective therapeutic medications are urgently needed. As reported previously, BD-604 is a fully human monoclonal antibody with strong in vitro and in vivo neutralizing activity to SARS-COV-2.
Objective: The purpose of this study was to characterize the pharmacokinetic properties of BD-604 in cynomolgus monkeys.
Methods: To analyze the concentration of BD-604 in cynomolgus monkey serum, an ELISA assay was established and a systemic validation was performed including accuracy and precision, dilution linearity and hook effect, selectivity, specificity, stability, and parallelism tests. Then, six naïve cynomolgus monkeys (3/sex) were administered BD-604 at a single dose of 10 mg/kg via intravenous infusion (60 minutes). Blood samples were collected at various time points (0-672 h) and analyzed for serum concentrations of BD-604.
Results: The data from validation experiments assure the reproducibility and reliability of the established ELISA assay. Then, the validated method was used to measure BD-604 concentration in cynomolgus monkey serum. The pharmacokinetics parameters including terminal half life (t[SUB]1/2[/SUB] ), peak serum concentration (C[SUB]max[/SUB] ), area under curve from time zero to last timepoint or infinity (AUC[SUB]last[/SUB] /AUC[SUB]inf[/SUB] ), apparent volume of distribution (V[SUB]z[/SUB] ), clearance rate (CL), and mean residence time (MRT) were calculated and reported. BD-604 showed no marked sex differences at the dose of 10 mg/kg when comparing the AUC[SUB]0-last[/SUB] and C[SUB]max[/SUB] between female and male cynomolgus monkeys.
Conclusion: In cynomolgus monkeys, BD-604 possesses pharmacokinetic properties similar to natural IgGs.
Keywords: Pharmacokinetics SARS-COV-2 BD-604 Monkey Monoclonal antibody.
. 2021 Jul 2.
doi: 10.1002/dta.3122. Online ahead of print.
Pharmacokinetic profiles of a SARS-COV-2 neutralizing antibody BD-604 in cynomolgus monkeys
Feng Gao[SUP] 1 [/SUP], Xu Zhang[SUP] 1 [/SUP]
Affiliations
- PMID: 34215019
- DOI: 10.1002/dta.3122
Abstract
Background: Currently, severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) has spread worldwide as a severe pandemic and effective therapeutic medications are urgently needed. As reported previously, BD-604 is a fully human monoclonal antibody with strong in vitro and in vivo neutralizing activity to SARS-COV-2.
Objective: The purpose of this study was to characterize the pharmacokinetic properties of BD-604 in cynomolgus monkeys.
Methods: To analyze the concentration of BD-604 in cynomolgus monkey serum, an ELISA assay was established and a systemic validation was performed including accuracy and precision, dilution linearity and hook effect, selectivity, specificity, stability, and parallelism tests. Then, six naïve cynomolgus monkeys (3/sex) were administered BD-604 at a single dose of 10 mg/kg via intravenous infusion (60 minutes). Blood samples were collected at various time points (0-672 h) and analyzed for serum concentrations of BD-604.
Results: The data from validation experiments assure the reproducibility and reliability of the established ELISA assay. Then, the validated method was used to measure BD-604 concentration in cynomolgus monkey serum. The pharmacokinetics parameters including terminal half life (t[SUB]1/2[/SUB] ), peak serum concentration (C[SUB]max[/SUB] ), area under curve from time zero to last timepoint or infinity (AUC[SUB]last[/SUB] /AUC[SUB]inf[/SUB] ), apparent volume of distribution (V[SUB]z[/SUB] ), clearance rate (CL), and mean residence time (MRT) were calculated and reported. BD-604 showed no marked sex differences at the dose of 10 mg/kg when comparing the AUC[SUB]0-last[/SUB] and C[SUB]max[/SUB] between female and male cynomolgus monkeys.
Conclusion: In cynomolgus monkeys, BD-604 possesses pharmacokinetic properties similar to natural IgGs.
Keywords: Pharmacokinetics SARS-COV-2 BD-604 Monkey Monoclonal antibody.