| The intravenous
and oral disposition of the antithyroid drug methimazole was determined
in 10 clinically normal cats and nine cats with naturally occurring hyperthyroidism.
After intravenous administration of 5 mg methimazole, the mean residence
time was significantly (P less than 0.05) shorter in the cats with hyperthyroidism
than in the normal cats, but there was no significant difference between
the mean values for total body clearance (CL), steady state volume of
distribution (Vdss), terminal elimination rate constant (ke), or serum
terminal half-life (t1/2) in the two groups of cats. After oral administration,
the mean bioavailability of methimazole was high in both the normal cats
(77.6 per cent) and cats with hyperthyroidism (79.5 per cent). The values
for mean residence time, ke and serum terminal t1/2 after oral dosing
were significantly shorter in the cats with hyperthyroidism than in the
normal cats. However, after oral administration of methimazole there were
no significant differences between the mean values for CL, Vdss, bioavailability
and maximum serum concentrations or the time for maximal concentrations
to be reached in the two groups of cats. Overall, most pharmacokinetic
parameters for methimazole were not altered by the hyperthyroid state.
However, the cats with hyperthyroidism did show a trend toward faster
elimination of the drug compared with the normal cats, similar to what
has been previously described for the antithyroid drug propylthiouracil
in cats. These results also indicate that methimazole is well absorbed
when administered orally and has a higher bioavailability than that of
propylthiouracil in cats with hyperthyroidism. Methimazole also has a
twofold longer mean serum terminal half-life than Propylthiouracil in
cats, which may account for the finding that methimazole is often effective
when administered less frequently than Propylthiouracil. |