| small molecule (SM) |
primarily oral |
often once a day |
generally good |
variable |
generally high; broad distribution to organs and tissues including
CNS |
primarily by CYP and phase II enzymes |
| bRo5 SM |
emerging examples of orally bioavailable |
daily to weekly |
few examples of orally bioavailable |
variable |
mostly peripheral distribution |
variable depending on functional groups |
| bRo5 cyclopeptides/macrocycles |
emerging examples of
orally bioavailable |
daily to weekly |
few
examples of orally bioavailable |
variable |
mostly peripheral distribution |
mainly proteolytic enzymes |
| large peptides |
not orally bioavailable;
mainly IV, SC |
weekly to monthly |
good for
SC |
variable |
peripheral distribution |
proteolytic enzymes |
| oligonucleotide
ASO |
not orally bioavailable; IV, SC, IT, and IVT |
weekly to monthly |
good for SC |
0.25–5 h after SC |
high; broad
distribution to kidneys and liver |
by nucleases |
| oligonucleotide siRNA |
not orally bioavailable;
IV, SC, IT, and IVT |
weekly to once every 3–6 months |
not reported |
not reported |
broad distribution to kidneys and
liver |
by nucleases |
| biologics
(antibodies) |
not orally bioavailable; mainly IV, SC,
and IM |
weekly to monthly |
good for SC and
IM |
1–8 days after
SC or
IM |
low; often limited to plasma and extracellular fluids |
catabolized by proteolytic enzymes |
