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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Pharmacokinetics and pharmacodynamics of the acetylcholinesterase inhibitor metrifonate in patients with renal impairment.

The aim of this study was to assess the influence of renal function on the pharmacokinetics, pharmacodynamics, safety, and tolerability of the acetylcholinesterase inhibitor metrifonate. Four groups of six age- and gender-matched subjects with varying degrees of renal function (creatinine clearances more than 90, 60-90, 30-60, and less than 30 mL/min/ 1.73 m2, respectively) were administered a single 50-mg oral dose of metrifonate. Blood and urine samples were collected for 24 hours and concentrations of metrifonate and its metabolites dichlorvos, dichloroacetic acid, and M3 were determined. Inhibition of acetylcholinesterase activity in erythrocytes and butyrylcholinesterase in plasma were also measured. Metrifonate was well tolerated in all treatment groups. The urinary excretion of metrifonate and dichlorvos decreased with decreasing renal function but accounted for less than 2% of the elimination. There were no statistically significant differences in primary pharmacokinetic parameters--Cmax, t(max), area under the concentration-time curve (AUC), and t1/2--of metrifonate and dichlorvos among the different groups. The excretion of dichloroacetic acid and M3 was not influenced by renal impairment. Acetylcholinesterase was not inhibited, whereas butyrylcholinesterase was inhibited markedly but independently of renal function. No metrifonate dose adjustments are needed when treating subjects with renal impairment.[1]

References

  1. Pharmacokinetics and pharmacodynamics of the acetylcholinesterase inhibitor metrifonate in patients with renal impairment. Dingemanse, J., Halabi, A., Kleinbloesem, C.H., Heinig, R., Blume, H. Therapeutic drug monitoring. (1999) [Pubmed]
 
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