title: Pharmacokinetics and pharmacodynamics of metrifonate in humans.
abstract: We studied the pharmacokinetics and pharmacodynamics [red blood cell (RBC) cholinesterase (ChE) inhibition] of metrifonate (MTF) and its active anti-ChE metabolite, dichlorvos (DDVP) in Alzheimer's disease (AD) patients and normal controls after oral MTF. In Study I conducted for 6 h, 3 patients with prior MTF exposure received oral MTF (7.5 mg/kg). Plasma ChE inhibition peaked to 78.5 +/- 12.3% at 15 min, while maximum RBC ChE inhibition seen at 1 h was 61.0 +/- 11.0%. Plasma ChE inhibition was unchanged at 6 h, whereas RBC ChE recovered with a t1/2 of 7.0 +/- 3.5 h. In Study II, 6 patients and 6 controls with no prior MTF exposure were given oral MTF. Mean plasma t1/2 of MTF was 2.3 +/- 0.3 h with ChE recovery t1/2 of 9.0 +/- 3.3 (plasma) and 26.6 +/- 15.2 days (RBC) after 7.5 mg/kg MTF. The short drug t1/2, long ChE recovery t1/2 and the achievement of high ChE inhibition levels with minimal side effects suggest the potential use of this drug for Alzheimer therapy.
authors.affiliation: Department of Psychiatry, Southern Illinois University School of Medicine, Springfield.
authors.forename: L K
authors.initials: LK
authors.lastname: Unni
authors.forename: C
authors.initials: C
authors.lastname: Womack
authors.forename: M E
authors.initials: ME
authors.lastname: Hannant
authors.forename: R E
authors.initials: RE
authors.lastname: Becker
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D002802:Cholinesterases / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004006:Dichlorvos / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D014236:Trichlorfon / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D004006:Dichlorvos; D014236:Trichlorfon; D002802:Cholinesterases