Pharmacokinetic modeling and quantitative prediction of subcutaneous absorption of antibody-based therapeutics – An update

Biologics

Therapeutic proteins

Protein therapeutics

Interspecies prediction

Routes of administration

Drug delivery

Model-informed drug development

ADA

anti-drug antibody

AUC

area under the concentration-time curve

BMI

body mass index

BSV

between-subject variability

Cavg

average drug concentration

CL

systemic clearance

Cmax

maximum drug concentration

Ctrough

trough drug concentration

CV

coefficient of variation

D

duration of zero-order input

EMA

European Medicines Agency

F

subcutaneous bioavailability

FcRn

neonatal Fc receptor

FDA

Food and Drug Administration

IgG

immunoglobulin G

IOV

inter-occasion variability

IV

intravenous

IVIVC

in vitro-in vivo correlation

ka

first-order absorption rate constant

ke

elimination rate constant

ktr

mean transit rate

mAb

monoclonal antibody

MIDD

model-informed drug development

mPBPK model

minimal PBPK model

MTT

mean transit time

PBPK model

physiologically-based pharmacokinetic model

pI

isoelectric point

PK

pharmacokinetic(s)

popPK model

population pharmacokinetic model

RMSE

root mean squared error

Q

intercompartmental clearance

rHuPH20

recombinant human hyaluronidase

R2

coefficient of determination

SC

subcutaneous

SC-PBPK model

PBPK model with the structure and kinetics at the level of the SC injection site and along the lymphatics described using physiological variables and processes

SCISSOR

subcutaneous injection site simulator

SD

standard deviation

Tlag

absorption lag time

Tmax

time to reach maximum drug concentration

TMDD

target-mediated drug disposition

t0.5,abs

absorption half-life

Vc

volume of central compartment

Vd

volume of distribution

Vp

volume of peripheral compartment.