mAbs Have an Extended Half-life, Allowing for Longer Dosing IntervalsThan Small Molecules

Administration and Pharmacokinetics1-3

Comparison of Simulated PK Profiles for a mAb (SC) and a Small-Molecule Drug (Oral)

Therapeutic mAbs are administered parenterally (IV, IM, or SC); oral delivery is not feasible because of gastrointestinal proteolytic degradation. Compared with small-molecule drugs, mAbs have an extended half-life, which may allow for longer dosing intervals.

IM, intramuscular; IV, intravenous; mAb, monoclonal antibody; PK, pharmacokinetics; SC, subcutaneous. Figure is for illustrative purposes only. Simulation based on PK concepts in1. Silberstein S, et al. Headache. 2015;55:1171-1182. 2. Dhillon S, et al. Clinical Pharmacokinetics. 2006. 3. Crommelin DJA, et al. Pharmaceutical Biotechnology: Fundamentals and Applications, 4th Edition. 2013.
mAbs &
small molecules

Summary of Differences Between mAbs and Small Molecules1

PropertySmall molecule mAb
Size~500 daltons~150,000 daltons
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.