Effects of the novel norepinephrine prodrug, droxidopa, on ambulatory blood pressure in patients with neurogenic orthostatic hypotension.
The prodrug droxidopa increases blood pressure (BP) in patients with neurogenic orthostatic hypotension. The BP profile of droxidopa in neurogenic orthostatic hypotension patients (n = 18) was investigated using ambulatory BP monitoring. Following dose optimization and a washout period, 24-hour "off-drug" data were collected. "On-drug" assessment was conducted after 4-5 weeks of droxidopa treatment (mean dose, 444 mg, three times daily). Ambulatory monitoring off drug revealed that 90% of patients already had abnormalities in the circadian BP profile and did not meet criteria for normal nocturnal BP dipping. On treatment, both overall mean 24-hour systolic and diastolic BPs were higher compared to off drug (137/81 mm Hg vs. 129/76 mm Hg; P = .017/.002). Mean daytime systolic BP was significantly higher with droxidopa (8.4 ± 3.1 mm Hg; P = .014). Although nocturnal BP was not significantly higher on droxidopa versus off treatment (P = .122), increases in nocturnal (supine) BP ≥10 mm Hg were observed in four cases (22%). Severe supine systolic hypertensive readings at night (>200 mm Hg) were captured in one case and only while on treatment. These data demonstrate that ambulatory BP monitoring is useful to evaluate the circadian BP profile after initiating treatment with a pressor agent.
Department of Neurology, New York University, New York, NY, USA. Electronic address: Horacio.Kaufmann@nyumc.org.
Horacio
H
Kaufmann
Department of Neurology, New York University, New York, NY, USA.
Lucy
L
Norcliffe-Kaufmann
Lundbeck, LLC, Deerfield, IL, USA.
L Arthur
LA
Hewitt
Lundbeck, LLC, Deerfield, IL, USA.
Gerald J
GJ
Rowse
Division of Hypertension and Clinical Pharmacology, Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, CT, USA.
William B
WB
White
D000368:Aged; D000369:Aged, 80 and over; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm / Q000502:physiology; D015103:Droxidopa; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007024:Hypotension, Orthostatic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D011355:Prodrugs; D014662:Vasoconstrictor Agents; D015103:Droxidopa; D009638:Norepinephrine
Circadian rhythm; clinical trials; supine hypertension