After
an intravenous administration of Propafenone (2
mg/kg) in ten minutes the drug plasma concentration
quickly increases, reaching a peak at the tenth
minute. Then it rapidly falls until
halving its value at the twentieth minute and
thereafter slowly decreases.(4)
To
maintain effective plasma levels, a maintenance
infusion is necessary after the intravenous bolus.
Propafenone
is completely
absorbed with peak plasma concentrations
occurring after 2-4 hours.
The
drug undergoes a hepatic first-pass
metabolism.
Two
metabolic phenotypes has been identified: extensive
and poor metabolisers.
Poor
metabolisers represent 5-10% of the
caucasian population.
Propafenone’s
plasma half-life after a single
administration is 5.5 ± 2.1 hours for
extensive metabolisers; for poor metabolisers it is
17.2 ± 8.0 hours. During long term treatment a
reduction in Propafenone clearance may be observed
with a subsequent increase in its plasma half-life.(5)
The
principal metabolite is 5-hydroxy-propafenone, which also
possesses an antiarrhythmic activity similar to that
of the parent compound but which has no ß-blocking
activity. The half-life of 5-hydroxy-propafenone in
extensive metabolisers is 5.5 hours (range: 2.6-9.9).
Steady
state plasma concentrations are reached in
3 - 5 days.
Therapeutic
plasma levels of Propafenone are reported to
fall within the range of 0.2 - 2 microg/ml, but the
correlation between Propafenone plasma concentrations
and antiarrhythmic efficacy is poor.
Propafenone
plasma
protein binding is about 95%.
A
little more than 50% of administered Propafenone is
eliminated in the faeces, and the remaining 50% in
the urine.
