Acute Effects of Oral Levodopa on Seated Mean Arterial Blood Pressure in Parkinson’s Disease
Catherine Liu1, Jeremiah Momper1, Kuldeep Mahato2, Chochanon Moonla2, Hamid Ghodsi3, Joseph Wang2, Irene Litvan3, Katherine Longardner3
1Skaggs School of Pharmacy and Pharmaceutical Sciences, 2Department of Chemical and Nano Engineering, University of California San Diego, 3Department of Neurosciences, University of California San Diego Parkinson and Other Movement Disorder Center
Objective:
Determine the acute effects of levodopa on blood pressure (BP) in persons with Parkinson’s disease (PwP).
Background:
Levodopa decreases BP in PwP [1-5]. This is thought to be due to a negative inotropic effect, either due to central sympathetic inhibition or peripheral cardiac effects [6]. Intravenous levodopa is associated with hypotension that correlates with better motor performance and higher levodopa levels [7], but no pharmacodynamic studies have determined oral levodopa’s effects on BP. Understanding this relationship is relevant to guide therapeutic decision-making, e.g., how aggressively to treat hypotension before initiating or increasing levodopa.
Design/Methods:
Using novel technology to measure levodopa from finger-pricked blood [8], we recruited PwP [9] taking oral carbidopa/levodopa with baseline BP ≥ 90/60 mmHg. Participants arrived after holding antiparkinsonian medications overnight. At time 0 they took carbidopa/levodopa instant-release tablets. Capillary blood levodopa levels, BP measurements (seated), and motor assessments using a modified Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part III [11] were performed at baseline and repeated every 10 minutes for 100 minutes. Non-compartmental pharmacokinetic parameters of levodopa were determined including AUC0→last, Cmax, Tmax (Phoenix WinNonLin v 8.4).
Results:
We enrolled 14 PwP (6 females, mean age 69.5 years, ± 7.6). Two had orthostatic hypotension, and six took antihypertensive medications. The mean arterial pressure (MAP = DBP + (SBP-DBP)/3) dropped over the course of the study visit for all participants, with an average of 105 mmHg ± 13.1 at baseline to a nadir of 74 mmHg ± 32.5. The average maximum drop in MAP occurred at 100 minutes post-dose and as mean AUC increases over time, mean MAP decreases.
Conclusions:
Oral levodopa is associated with acute hypotension in PwP, and levodopa exposure and MAP are inversely correlated. These effects should be considered when adjusting levodopa doses, especially in people with hypotension, to improve safety outcomes.
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