Drug Half-Life

Drug Half-Life (\(T_{1/2}\) in most Assess models), is the half-life of the non-specific elimination of the drug, or the time it takes for the concentration of a drug to be reduced by half as a result of non-specific uptake and metabolic degradation while excluding all other sources of drug clearance including receptor mediated internalization and subsequent degradation. The processes encapsulated by this parameter are generally not saturable at therapeutic doses, thus the half-life is fixed and not dose- or drug-concentration dependent.

This half-life is distinct from the observed half-life in pharmacokinetic data, which may result from a mix of non-specific and target mediated clearance mechanisms. The units for half-life are days and the longer the half-life the slower the degradation of the drug.

Drug Half-Life in Assess

Antibody or antibody-like biotherapeutics generally have predictable linear pharmacokinetic (PK) properties. (Deng et al 2011, Dong et al. 2011, Betts et al. 2018) In the absence of direct measurements, typical values from clinical antibodies can be used. The half-life can also be measured in preclinical species and allometrically scaled to predict human PK. (Betts et al. 2018)

Typical Values for Antibodies

Species	\(T_{1/2}\) (day)	References
Mouse	6.3	Deng et al. 2011; Avery et al. 2016
Rat	3.6	Deng et al. 2011
Cyno	7	Betts et al. 2018; Singh et al. 2015; Deng et al. 2011
Human	15	Dirks and Meibohm 2010; Betts et al. 2018; Davada et. al.; Singh et al. 2015