Applicability of surrogate approach of free drug equilibrium between plasma and tissues for different modalities

Type of ModalitiesApplicabilityExamplesKp or Kp, uuComments
Highly permeable compoundsYes, in bloodEliquis=1As many other small molecules
Efflux transporter substratesNo, in brain or fetusEliquis>1 or <1Low concentration in brain but high in milk
Uptake transporter substratesNoStatins>1Liver OATP uptake
Quick-forming prodrugsMaybeOseltamivir>1Hydrolysis removal of protecting groups
Lysosomal trappingCould beGarenoxacin>1, =1pH gradient, lysosomal accumulation into macrophages
Target trappingNot likelyPaclitaxel>>1Microtubule binding, cancer cell accumulation
Covalent bindersNot likelyAfatinib>1DNA alkylators, protein modifiers
Transforming prodrugsNoTenofovir>>1Active drug formed through metabolism and biosynthesis in tissue
ADCsNoKadcyla>>1Antigen-mediated uptake, catabolism, drug release
Nucleic acidNoFomivirsen Mipomersen>1Unique distribution properties
NanoparticlesNo>>1Unique distribution properties
InhalationNoFluticasone>>1Designed to increase systemic clearance
  • ADC, antibody drug conjugate; OATP, organic-anion-transporting polypeptide.