Plasma Levels of Metrifonate and Dichlorvos during Treatment of Schistosomiasis with Bilarcil®

Humans appear no more sensitive than laboratory animals to the inhibition of red blood cell cholinesterase by dichlorvos

“…Data are also available from studies conducted in diverse clinical populations. These include studies of the clinical efficacy of DDVP as an anti-worming drug in patients infected with parasites (Cervoni et al, 1969;Pena Chavarria et al, 1969), the use of registered DDVP resin strip products in hospital settings (Cavagna et al, 1969(Cavagna et al, , 1970Vigliani, 1971), the clinical use of metrifonate for schistosomiasis in infected children and adults (Maxwell et al, 1981;Nordgren et al, 1980Nordgren et al, , 1981Reiner and Plestina, 1979), and the potential uses of metrifonate for treatment of AlzheimerÕs disease in aged and sick subpopulations (Becker et al, 1990(Becker et al, , 1996(Becker et al, , 1998Cummings et al, 1998;DuBois et al, 1999). Most patients have not demonstrated enhanced sensitivity to DDVP relative to healthy subjects (Cavagna et al, 1969;Cervoni et al, 1969;Pena Chavarria et al, 1969).…”

“…Studies have shown that DDVP is rapidly absorbed, distributed, and metabolized in both animals and humans (e.g., Blair et al, 1975;Nordgren et al, 1980Nordgren et al, , 1981. None of the data available for review indicated that different species handle DDVP differently following either oral or inhalation exposure.…”

A multicentre, randomized, double-blind, placebo-controlled study to evaluate the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate Alzheimer's disease: the MALT study

“…Third, metrifonate has an inbuilt, up-titration mechanism (Schmidt, 1996;Hinz, 1996a, b), as repeated dosing results in a gradual increase in AChE inhibition towards target levels (Heinig, 1997), an eect achieved with short-acting reversible inhibitors only by progressive dose titration. Fourth, in contrast to the long-lasting enzyme inhibition, both metrifonate and DDVP have very short plasma half-lives and are rapidly removed from the body (Nordgren, 1980). Therefore, high levels of AChE inhibition can be reached without compromising the tolerability of the compound.…”

The Pharmacological Basis for Metrifonate’s Favourable Tolerability in the Treatment of Alzheimer’s Disease

“…Metrifonate has a short terminal half-life of 1.7-2.2 h in elderly volunteers and Alzheimer patients [4,8] and DDVP blood concentrations decline in parallel to those of metrifonate [8,22,23]. At any time, the blood levels of DDVP are approximately 2% of those of metrifonate [4,24].…”