mAbs Can Have a Low Potential for Drug-Drug Interactions


mAbs Do Not Undergo Hepatic Metabolism and Are Therefore Not Subject to Significant Drug-Drug Interactions

Small Molecule Elimination1

Small molecules are generally metabolized and eliminated through hepatic, renal, and biliary mechanisms. Many small molecules are metabolized by cytochrome P450 enzymes into chemical entities. This process may result in significant interactions with other medications.

mAb Elimination1-3

Antibodies are internalized and broken down into peptides and amino acids through the reticuloendothelial system or target-mediated elimination. They are not subject to significant interaction with other medications.

mAb, monoclonal antibody.1. Foltz IN, et al. Circulation. 2013;127:2222-2230. 2. Silberstein S, et al. Headache. 2015;55:1171-1182. 3. Goel G, et al. J Hematol Oncol. 2015;8:92.
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.