What Do Oral Drugs Really Look Like? Dose Regimen, Pharmacokinetics, and Safety of Recently Approved Small-Molecule Oral Drugs

An analysis of dose, dose frequency, human pharmacokinetics, and potential drug–drug interactions (DDI) was performed on small-molecule oral drugs approved by the FDA from 2020 to 2024 (n = 104). Although most oral drugs are administered QD (67%), BID and TID regimens are also regularly approved (32%). First-in-class (FIC) drugs and drugs with Orphan Drug Designation (ODD) have a higher frequency of BID or TID administration compared to drugs without those designations (BID and TID = 50% for FIC drugs vs 19% for non-FIC; BID and TID = 41% for ODD vs 20% non-ODD). Most drugs are >95% plasma protein bound (58%), with a large fraction >99% bound (29%). Of these drugs, 22% have black box warnings and 42% list contraindications. An examination of DDI revealed the most frequent warning around CYP3A4 induction (60%). These findings will help medicinal chemists better understand and predict typical and nontypical profiles of oral drugs.