Pharmacokinetics (PK)/Toxicokinetics (TK)

Research on Gyrolab platform at nanoliter-scale reduces sample requirements and animal use.

Three full PK profiles from three rodents; IV administration of a therapeutic antibody.  Data courtesy of Astra Zeneca.Pharmacokinetic (PK) bioanalysis presents challenges at all stages of development for the safety and efficacy of biologics. Early in development, there is a need to support multiple candidates and multiple programs. Preclinical development is subject to aggressive timelines and large sample numbers in a variety of species with limited volumes for both samples and reagents. In regulated bioanalysis, more robust methods with higher throughput are essential for decisions in advancing project timelines. Application of Gyros’ technology platform for PK bioanalysis provides versatility and flexibility at all stages in an automated, nanoliter-scale format.

Gyrolab benefits for pharmacokinetic studies:

  • Broader dynamic ranges
    Reduces sample dilutions with minimal matrix interference to avoid analyte/sample bias or error
  • Shorter time to results
    Enables faster decisions for study/assay development support
  • Reduced volumes
    Enables serial sampling to obtain a PK profile from a single mouse
  • Automated
    Increases method robustness and unattended runs to shorten project timelines

Discovery PK

In discovery, a flexible assay design is critical to support multiple species and programs with large numbers of samples, conditions and limited reagents. Generic PK assays allow for a platform approach to quantitate multiple human Abs in animal sera while reducing assay development time and increasing automated throughput capacity for proof of concept and rapid assessment of lead candidate identification and optimization. Automation of the assay workflow also removes cumbersome manual or liquid handling setups. In some instances, multiple assays/conditions are run in parallel or on different segments within the CD consumable to allow comparative data for different formats and leads.

Application of miniaturized immunoassays to discovery pharmacokinetic bioanalysis.
Roman J, Qiu J, Dornadula G, Hamuro L, Bakhtiar R, Verch T.
J Pharmacol Toxicol Methods. 2011 May-Jun;63(3):227-35. doi: 10.1016/j.vascn.2010.12.002. Epub 2010 Dec 13.

One mouse, one PK profile

Gyrolab systems’ nanoliter volume requirements enable an entire PK from a single mouse which significantly reduces the number of mice used and the biological variability of PK endpoints. Obtaining a PK profile from a single mouse using serial sampling is an animal sparing strategy consistent with the 3R research initiative that has been established at multiple biopharmaceutical companies with the Gyrolab platform. This strategy reduces the number of mice needed by 60-80% which not only improves data quality but impacts cost reductions in maintaining animal colonies, husbandry needs/facilities and removal of biological wastes. The ability to execute a one mouse, one PK profile strategy on Gyrolab platforms is especially useful when test articles are in short supply, rank ordering of PK with more than three test articles and with rare animal disease models.

One mouse, one pharmacokinetic profile: quantitative whole blood serial sampling for biotherapeutics.
Joyce AP, Wang M, Lawrence-Henderson R, Filliettaz C, Leung SS, Xu X, O’Hara DM.
Pharm Res. 2014 Jul;31(7):1823-33. doi: 10.1007/s11095-013-1286-y. Epub 2014 Jan 24.

Regulated PK bioanalysis

Regulated bioanalysis in support of GLP PK studies and clinical trials require increased method robustness as these assays are continually validated and used for long-term study support. GLP studies have a variety of safety toxicology and DMPK endpoints for a multitude of conditions that are required for at least one rodent specie and another relevant animal specie. Regulated bioanalysis for PK clinical trials are long term studies requiring assay robustness and reliability typically demonstrated by assay and in-study validation such as incurred sample reanalysis. Automation of PK bioanalysis on Gyrolab platforms provide higher throughput, minimal staffing, analysis time and reduces the manual sources of error that improve overall method robustness and facilitates assay transfer to CROs.

Read interview with Shawn Fernando, Morphotek Inc., on high-throughput PK assays in Phase II/III trials >

A randomised, double-blind, multicentre, parallel-group, prospective study comparing the pharmacokinetics, safety, and efficacy of CT-P13 and innovator infliximab in patients with ankylosing spondylitis: the PLANETAS study
Ann Rheum Dis 2013;72:1605-1612 doi:10.1136/annrheumdis-2012-203091