Objective: To investigate changes in Levodopa (LD) pharmacokinetics and changes in homocysteine, vitamin B6, and vitamin B12 in Parkinson’s disease (PD) patients receiving LD formulations when LD/DCI formulations are combined with catechol-O-methyltransferase (COMT) inhibitors (COMT-I).

Background: LD replacement therapy is a mainstay of PD treatment. Administered LD is metabolized to dopamine by dopa decarboxylase (DDC) in the gastrointestinal tract and to 3-O -methyldopa (3-OMD) by COMT. Predominant use of chronic dopa decarboxylase inhibitor (DCI) results in COMT-mediated metabolism yet this process requires methyl groups from a methionine circuit. A methionine circuit produces homocysteine and consumes B vitamins. The authors hypothesized that high COMT activity would result in elevated homocysteine and declined vitamin B6, vitamin B12 and folate, and that concomitant use of COMT-I would suppress these changes.

Method: We compared pharmacokinetics of LD and 3-OMD with those of vitamin B6, vitamin B12, folate, and homocysteine in 110 PD patients (49 males and 61 females) attending our institution during oral administration of fixed-dose LD/DCI, with and without oral COMT-I (Entacapone and Opicapone). LD and its metabolites were determined by high-performance liquid chromatography (HPLC).

Results: Comparing the low vitamin B6 group (28 patients) with the normal group (82 patients), the low group had significantly higher daily LD dose (621±226 mg vs. 491±202 mg, p<0.05) and lower ALT levels (6.86±6.56 IU/l vs. 11.95±7.41 IU/l, p<0.05). In the COMT-I oral group (30 patients) versus the non-oral group (80 patients), the oral group had a significantly higher daily LD dose (593±206 mg vs. 498±214 mg, p<0.05), a significantly higher plasma LD concentration (7034±4852 pmol/ml vs. 3755±3014 pmol/ml, p<0.05) and a significantly lower 3-OMD ( 7365±9718 pmol/ml vs 18068±12723 pmol/ml, p<0.05). However, there was no significant difference in vitamin B6 between the COMT-I oral and non-oral groups.

Conclusion: Our comparative study of LD and 3-OMD pharmacokinetics and vitamin levels in Japanese PD patients with and without concomitant COMT-I during oral administration of LD/DCI combination drugs revealed that vitamin B6 decreased with higher daily LD dose though concomitant use of a COMT-I reduced vitamin B6 consumption.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/combination-comt-inhibitor-with-levodopa-reduces-consumption-of-vitamin-b6/