Type of Modalities | Applicability | Examples | Kp or Kp, uu | Comments |
---|---|---|---|---|
Highly permeable compounds | Yes, in blood | Eliquis | =1 | As many other small molecules |
Efflux transporter substrates | No, in brain or fetus | Eliquis | >1 or <1 | Low concentration in brain but high in milk |
Uptake transporter substrates | No | Statins | >1 | Liver OATP uptake |
Quick-forming prodrugs | Maybe | Oseltamivir | >1 | Hydrolysis removal of protecting groups |
Lysosomal trapping | Could be | Garenoxacin | >1, =1 | pH gradient, lysosomal accumulation into macrophages |
Target trapping | Not likely | Paclitaxel | >>1 | Microtubule binding, cancer cell accumulation |
Covalent binders | Not likely | Afatinib | >1 | DNA alkylators, protein modifiers |
Transforming prodrugs | No | Tenofovir | >>1 | Active drug formed through metabolism and biosynthesis in tissue |
ADCs | No | Kadcyla | >>1 | Antigen-mediated uptake, catabolism, drug release |
Nucleic acid | No | Fomivirsen Mipomersen | >1 | Unique distribution properties |
Nanoparticles | No | >>1 | Unique distribution properties | |
Inhalation | No | Fluticasone | >>1 | Designed to increase systemic clearance |
ADC, antibody drug conjugate; OATP, organic-anion-transporting polypeptide.