Effects of L-threo-3,4-dihydroxyphenylserine on orthostatic hypotension in hemodialysis patients.
BACKGROUND
Orthostatic hypotension (OH) is a serious complication observed in hemodialysis (HD) patients after HD as well as during the interdialytic period. L-Threo-3,4-dihydroxyphenylserine (L-DOPS) is a nonphysiological neutral amino acid that is directly converted to the neurotransmitter norepinephrine by aromatic L-amino acid decarboxylase.


METHODS
A placebo-controlled double-blind study for 4 consecutive weeks and a long-term study (24-52 weeks) were conducted to evaluate the efficacy of L-DOPS for OH after HD. The drug was administered orally 30 min before the start of each HD period in both studies. Doses of 400 mg of L-DOPS or placebo were given to HD patients with OH (45 and 41 patients, respectively) in the double-blind study, and doses of 200 or 400 mg of L-DOPS were given to 74 HD patients in the long-term study.


RESULTS
In the double-blind study, L-DOPS significantly ameliorated subjective symptoms related to OH, including dizziness/light-headed feeling, and malaise, throughout the interdialytic period. For 19 patients with delayed-type OH, hypotension with the lowest blood pressure recorded 10 min after standing, the decrease in blood pressure was suppressed significantly after L-DOPS treatment (10 patients) as compared with the placebo-treated group (9 patients). In the long-term study, the efficacy of L-DOPS was not attenuated, and the marked fluctuations in the plasma L-DOPS and norepinephrine levels were not noted after long-term use, without increases in incidence or severity of adverse reactions.


CONCLUSIONS
These results indicate that L-DOPS is effective for improving OH-related interdialytic subjective symptoms in HD patients after short-term as well as after long-term administration.
Iida
Nobutoshi
N
Yodogawa Christian Hospital, Awaji, Higashiyodogawa-ku, Osaka, Japan. nobu1114@pearl.ocn.ne.jp
Koshikawa
Syozo
S
Akizawa
Tadao
T
Tsubakihara
Yoshiharu
Y
Marumo
Fumiaki
F
Akiba
Takashi
T
Kawaguchi
Yoshindo
Y
Imada
Akio
A
Yamazaki
Chikao
C
Suzuki
Masashi
M
D001342:Autonomic Nervous System Diseases / Q000188:drug therapy / Q000503:physiopathology; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015103:Droxidopa / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007024:Hypotension, Orthostatic / Q000097:blood / Q000188:drug therapy* / Q000209:etiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects*; D013223:Statistics as Topic / Q000379:methods
D002317:Cardiovascular Agents; D015103:Droxidopa; D009638:Norepinephrine