Attribute | SMD | mAb | ADC |
---|---|---|---|
MW (Da) | Typically <1 K | ∼150 K | ∼150 K |
Dosing route | Typically Oral | Subcutaneous or intravenous | Intravenous |
Distribution | High Vd and well perfused into tissues; potential substrate of transporters | Vd close to plasma volume; limited tissue distribution | ADC similar to mAb; unconjugated drug similar to SMD |
Metabolism | Mainly phase I and II metabolism | Catabolism | Both |
Excretion | Mainly biliary and renal excretion | Mostly recycled by body | Both |
Circulation half-life | Typically short (hours) | Long (days) | Long for both ADC and unconjugated drug (days) when dosed as ADC |
PK linearity | Usually linear at low dose and nonlinear at high dose | Usually linear at high dose and nonlinear at low dose | Similar to mAb |
PK analytes | Drug and metabolites | Antibody | ADC or conjugated drug, total antibody, and unconjugated drug |
Analytical methods | Typically LC-MS/MS | Typically ligand binding assays | Both |
Immunogenicity | No | Yes | Yes |
API heterogeneity | Uniform single entity | Generally uniform | Mixture of ADCs with different DAR |
API, active pharmaceutic ingredient; LC-MS/MS, liquid chromatography with tandem mass spectrometry; MW, molecular weight; Vd, volume of distribution.