Which is more harmful C/L ER or C/L + COMT inhibitor

[gesundheight]

C/L does good job in relieving PD symptoms. But the benefits come at a cost. Which is in the process of synthesizing Levodopa into dopamine in the brain hydroxy free radicals get generated according to scientific literature, which contributes to the progression of the disease. While COMT inhibitors inhibit COMT enzymes. COMT is an important process for eliminating toxic or biologically active catechols and other hydroxylated metabolites. Using COMT inhibitors for long time could lead to liver failure. C/L extended release means more levodopa into the brain over extended period of time. If you suffer from fluctuations which treatment would you choose C/L ER, or C/L + COMT?

[park_bear]

I use both

pubmed.ncbi.nlm.nih.gov/111...

"In contrast, clinical trials with entacapone demonstrated no increase in liver enzymes above those observed with placebo. Further, no instances of acute liver failure or death attributed to the drug have been observed in post-marketing surveillance studies. Consequently, liver monitoring is not required with this agent. These data demonstrate that tolcapone is associated with a risk of hepatotoxicity but that no such risk has been detected with entacapone."

Regarding: >"the process of synthesizing Levodopa into dopamine in the brain hydroxy free radicals get generated according to scientific literature, which contributes to the progression of the disease. "

link.springer.com/article/1...

Disease Progression and Pharmacodynamics in Parkinson Disease – Evidence for Functional Protection with Levodopa and Other Treatments

From the full text which is behind a paywall:

"Despite concerns (1,36) about levodopa worsening disease progression there was no suggestion that levodopa accelerated the rate of progression in this DATATOP cohort which confirms earlier findings (35). Indeed levodopa appeared to have a protective effect. In vivo animal studies and clinical studies have failed to demonstrate an unequivocal toxic effect of levodopa (37,38). Rather than a neurotoxic effect of levodopa, we found evidence for a robust functional neuroprotective effect."