Jeffreyn,

Thanks for your prompt reply.

I agree when you write:
"- if you don't add a DDC inhibitor (i.e. carbidopa/benserazide), you need to use a much larger dose of levodopa, in order for sufficient levodopa to make it into the brain;
- such large doses of levodopa cause unwanted side effects (e.g. nausea)."

You write:
"My understanding regarding COMT inhibitors is that their main function (in PD treatment) is to (try to) stop COMT from breaking down dopamine in the brain."

I'm not familiar with this process. However, what you describe is the role played by MAO-B inhibitors (e.g. rasagiline) [1].
"Selective MAOB inhibitors ... preferentially [inhibit] MAOB, which mostly metabolizes DA. If MAOB is inhibited, then more DA is available for proper neuronal function, especially in Parkinson's Disease.

In a recent doctorial thesis [2] I've found a reference to the effect of levodopa plus entacapone without carbidopa:
"That the Cmax and AUC of levodopa in both CSF and blood increased significantly when additional entacapone was given alone and in combination with carbidopa. The increase was more evident when entacapone was combined with carbidopa."

Reference:

[1] Monoamine oxidase B - Wikipedia

[2] "Levodopa pharmacokinetics-from stomach to brain"
Maria Nord,
Dissertation, Linkoping University, 2017
https://liu.diva-portal.org/smash/ge...FULLTEXT01.pdf

John