Pharmacokinetic studies of oral L-threo-3,4-dihydroxyphenylserine in normal subjects and patients with familial amyloid polyneuropathy.
The pharmacokinetics of oral L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was studied in 7 normal subjects and 7 patients with familial amyloid polyneuropathy. Each person swallowed a single 300 mg dose in the fasting state, and L-threo-DOPS in plasma and urine was determined by high performance liquid chromatography with an electrochemical detector after separation on a boric acid gel column. L-threo-DOPS was slowly absorbed by normal subjects; the maximum plasma concentration occurred 3 h after administration and 20% of the oral dose was recovered unchanged in the urine within 12 h. It induced a substantial elevation of plasma norepinephrine levels, the peak being attained at 5 h, but without any change in blood pressure. In the patients, the absorption and metabolism of L-threo-DOPS were delayed, and a prolonged pressor response was observed, with a peak after 8 h. It was concluded that the effects on plasma norepinephrine and blood pressure of oral L-threo-DOPS were essentially equal to those of twice as large a dose of DL-threo-DOPS.
D000328:Adult; D000686:Amyloidosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D004299:Dopamine beta-Hydroxylase / Q000097:blood; D015103:Droxidopa / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008676:Metanephrine / Q000652:urine; D008875:Middle Aged; D009422:Nervous System Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D009647:Normetanephrine / Q000652:urine; D012694:Serine / Q000031:analogs & derivatives*; D013997:Time Factors
D009647:Normetanephrine; D012694:Serine; D008676:Metanephrine; D004299:Dopamine beta-Hydroxylase; D015103:Droxidopa; D009638:Norepinephrine