Intranasal L-threo-3,4,-dihydroxyphenylserine in treating diarrhea associated with familial amyloidotic polyneuropathy.
We evaluated the absorption disturbance of the gastrointestinal tract in patients with familial amyloidotic polyneuropathy (FAP). Ursodeoxycholic acid (UDCA) 300 mg was administered orally to 10 patients with FAP and 11 control subjects. Serum levels of total bile acid were determined as an indicator of absorption. The patients had lower serum levels of total bile acid than controls, suggesting an absorption disorder. To attempt to treat the diarrhea commonly associated with FAP, L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a synthetic precursor of norepinephrine, was administered 100 mg/dose by the oral and 8 mg/0.4 ml by the intranasal route and their effects on the elevation of serum norepinephrine levels were compared. The 3-0-monohemiphthalate salt of glycyrrhizinic acid and sodium ascorbate were used as vehicles for the intranasal preparation to enhance drug absorption and prevent oxidation. Increased serum levels of norepinephrine, the converted metabolite of L-threo-DOPS in serum, was observed 2 hours after intranasal administration, but not after administration of the oral preparation or vehicle alone. Intranasal administration of 8 mg 3 times/day for 1 week resulted in reduction of the daily frequency of diarrhea as well as a decrease in the severe orthostatic hypotension in three patients with FAP. Thus, an intranasal delivery system for L-threo-DOPS, which acts by stimulating adrenergic receptors, may be considered in treating patients with FAP with severe diarrhea.
Ando
Y
Y
First Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
Gotoh
T
T
Kawaguchi
Y
Y
Tanaka
Y
Y
Sakashita
N
N
Ando
M
M
D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D017772:Amyloid Neuropathies / Q000150:complications*; D001647:Bile Acids and Salts / Q000097:blood; D003967:Diarrhea / Q000150:complications / Q000188:drug therapy*; D004064:Digestive System / Q000378:metabolism*; D015103:Droxidopa / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D013997:Time Factors; D014580:Ursodeoxycholic Acid
D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid; D015103:Droxidopa; D009638:Norepinephrine