Oral Bioavailability of Monoclonal Antibody.

Area of Science:

• Pharmacokinetics
• Drug Delivery
• Biotechnology

Background:

• Oral delivery of monoclonal antibodies (mAbs) is of significant interest.
• The oral bioavailability of mAbs has not been previously determined.
• A preclinical study was designed to address this knowledge gap.

Purpose of the Study:

• To determine the absolute oral bioavailability of a monoclonal antibody (mAb) in preclinical models.
• To investigate the pharmacokinetics of orally administered mAbs.
• To establish a baseline for oral mAb absorption.

Main Methods:

• A humanized mAb (trastuzumab) was administered orally to mice and rats at 100 mg/kg.
• Plasma pharmacokinetics (PK) were measured over 14 days.
• Non-compartmental analysis (NCA) and compartmental modeling were used to estimate oral bioavailability.

Main Results:

• Oral bioavailability of mAb in rats was 0.027% (NCA) and 0.025% (modeling).
• Oral bioavailability of mAb in mice was 0.014% (NCA) and 0.013% (modeling).
• Absorption rate from the gastrointestinal tract was consistent between species (0.78 h⁻¹).

Conclusions:

• The oral bioavailability of humanized mAbs in rodents is approximately 0.02%.
• This suggests only 1 in 5000 orally administered mAb molecules reach systemic circulation.
• This is the first study reporting an absolute oral bioavailability for a mAb, with further research needed for generalizability.