Acute Pharmacodynamic Effects of Oral Levodopa on Blood Pressure in Parkinson's Disease

Levodopa decreases blood pressure (BP) in persons with Parkinson's disease (PwP), but no pharmacodynamic studies integrating systemic levodopa concentration measurements have characterized its hypotensive effects. Understanding this relationship is clinically relevant for guiding therapeutic decisions, such as how aggressively to treat hypotension before initiating or increasing levodopa. In this pilot study, we aimed to determine the acute pharmacodynamic effects of oral immediate-release carbidopa/levodopa on BP in PwP.

PwP taking chronic oral carbidopa/levodopa with baseline BP ≥ 90/60 mmHg were recruited. Participants withheld antiparkinsonian medications overnight prior to the study visit and received carbidopa/levodopa immediate-release tablets at time 0. Capillary blood levodopa levels, seated BP measurements, and motor symptom assessments were performed at baseline and repeated every 10 min for 70-100 min. Non-compartmental pharmacokinetic parameters of levodopa were determined, including the area under the curve up to the last time point (AUC_{0 → last}), maximum concentration (C_max), and time to maximum concentration (T_max).

Fourteen PwP were enrolled (mean age 69.5 ± 7.6 years, six females). Two participants had orthostatic hypotension at baseline (defined as a sustained drop in systolic BP ≥ 20 mmHg or diastolic BP ≥ 10 mmHg within 3 min of standing), and six were taking antihypertensive medications. Mean arterial pressure (MAP) declined during the study from an average of 105 ± 13.1 mmHg at baseline to a nadir of 84 ± 15.8 mmHg. The maximum MAP drop occurred at 100 min post-dose. Cumulative levodopa AUC negatively correlated with MAP (Pearson's r = -0.30; p = 0.00036).

Oral levodopa is associated with acute hypotension in PwP, and levodopa exposure is inversely correlated with MAP. These effects should be considered when adjusting levodopa dosing, particularly in patients with hypotension, to improve safety outcomes.