Pharmacokinetics and pharmacodynamics of metrifonate in humans

Methods Find Exp Clin Pharmacol. 1994 May;16(4):285-9.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Cholinesterases / blood*
  • Chromatography, High Pressure Liquid
  • Dichlorvos / blood
  • Dichlorvos / pharmacokinetics
  • Dichlorvos / pharmacology
  • Female
  • Half-Life
  • Humans
  • Male
  • Middle Aged
  • Trichlorfon / blood
  • Trichlorfon / pharmacokinetics*
  • Trichlorfon / pharmacology*

Substances

  • Dichlorvos
  • Trichlorfon
  • Cholinesterases