mAbs Have Minimal Distribution in the CNS Because of the Blood-Brain Barrier1


mAbs Are Largely Confined to the Vasculature, With Variable Distribution Across Tissue Types2

mAb Biodistribution Across Various Tissues3

mAb Tissue Biodistribution* Percentage of Plasma Concentration

Adapted from Duan X, et al. Anal Chem. 2012;84:4373-4382.

The distribution of mAbs depends on the extent to which they can cross the capillary endothelium.2 mAbs do not readily cross the intact blood-brain barrier.

CNS, central nervous system; Ig, immunoglobulin; mAb, monoclonal antibody.
*Figure demonstrates distribution of a murine IgG1 mAb in wild-type mice after intraperitoneal administration;
results may not be representative of all mAbs.3 1. Foltz IN, et al. Circulation. 2013;127:2222-2230. 2. Silberstein S, et al. Headache. 2015;55:1171-1182. 3. Duan X, et al. Anal Chem. 2012;84:4373-4382.
mAbs &
small molecules
Antibody-based
therapeutics

Summary of Differences Between mAbs and Small Molecules1

PropertySmall molecule mAb
Size~500 daltons~150,000 daltons
SpecificityLowerHigh
MetabolismHepatic/RenalReticuloendothelial system,
target-mediated disposition
ToxicityBroken down into chemical metabolites;
often cleared by liver or kidneys
On-target (depends on the target of the mAb)
and off-target toxicities (eg, immunogenicity)
Drug-drug interactionsMore likelyLess likely
Crossing blood-brain barrier2Potentially yes*Minimal
AdministrationUsually oralIntramuscular, subcutaneous,
or intravenous
Half-life3~HoursDays to weeks
DosingUsually dailyTypically less frequent (eg, monthly)
Production4,5Chemical synthesis; relatively easy
to make and reproduce reliably
Produced inside unique line of modified living
cells; difficult to make and reproduce precisely

*Depending on degree of lipid solubility.

mAb, monoclonal antibody.
1. Foltz IN, et al. Circulation. 2013;127:2222-2230. 2. Tabrizi M, et al. AAPS J. 2010;12:33-43. 3. Silberstein S, et al. Headache. 2015;55:1171-1182. 4. Kleinberg M, et al. Am J Health
Syst Pharm. 2004;61:695-710. 5. Committee on Methods of Producing Monoclonal Antibodies. Monoclonal Antibody Production. 1999.

Antibody-Based Therapeutics

Research and Development of mAbs Is Rapidly Evolving

The First mAb Was Produced in 1975; Since Then1

mAb, monoclonal antibody.
1. Silberstein S, et al. Headache. 2015;55:1171-1182. 2. Cai HH. MOJ Immunology. 2017;5:145. 3. Foltz IN, et al. Circulation. 2013;127:2222-2230.