Use of bromide as an anticonvulsant for dogs with epilepsy.
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Animals↗
Biomedical subjects
L A Trepanier
Publications and source records attributed to L A Trepanier.
Pharmacokinetic properties of bromide in dogs after the intravenous and oral administration of single doses.
Bromide (20 mg kg-1) was administered intravenously and orally to normal beagle dogs. The mean (SD) apparent elimination half life (t1/2 beta) after oral administration (46 +/- 9 days) was not significantly different from the mean t1/2 beta after intravenous administration (37 +/- 10 days). The mean total body clearance was 9.0 +/- 3.9 ml day-1 kg-1 and the mean apparent volume of distribution was 0.45 +/- 0.07 litre kg-1. The mean area under the serum concentration time curve (AUC) was significantly smaller after oral administration than after intravenous administration, and from a comparison of the two values the oral bioavailability of bromide was estimated to be 46 per cent. Assuming this degree of bioavailability, the daily dose of bromide necessary to maintain serum bromide concentrations within the therapeutic range of 1000 to 2000 mg litre-1 recommended for epileptic dogs was estimated to be approximately 21 mg kg-1. The intravenous loading dose of sodium bromide necessary to reach minimal therapeutic serum bromide concentrations was predicted to be 570 +/- 90 mg kg-1.
Administration, Oral↗
Effect of dietary chloride content on the elimination of bromide by dogs.
The effect of dietary chloride content (0.2, 0.4 and 1.3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg-1) was evaluated in normal beagles. Increasing the dietary chloride content from 0.2 to 1.3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 +/- 22 days to 24 +/- 7 days. The mean area under the concentration curve (AUC) for dogs fed 1.3 per cent chloride was significantly smaller than the AUC for dogs fed 0.2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (Cmax) or on the time (Tmax) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg-1 of bromide were significantly lower in dogs fed 1.3 per cent chloride (310 +/- 150 mg litre-1) than in dogs fed 0.2 per cent chloride (1950 +/- 1140 mg litre-1). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1.3 per cent chloride (43 +/- 13 mg kg-1) were almost twice as high as the dose estimated for dogs fed 0.4 per cent chloride (22 +/- 3 mg kg-1) and nearly three times as high as the dose estimated for dogs fed 0.2 per cent chloride (15 +/- 4 mg kg-1). These differences were statistically significant (P = 0.002).
Animals↗
Pharmacokinetics of methimazole in normal cats and cats with hyperthyroidism.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorption↗
Pharmacokinetics of intravenous and oral methimazole following single- and multiple-dose administration in normal cats.
The pharmacokinetics of methimazole (MMI) administered intravenously and orally were determined in six adult domestic shorthaired cats. There was no significant difference between mean serum MMI concentrations after oral and i.v. administration by 30 min post-MMI administration, indicating relatively rapid and complete absorption of the drug. The bioavailability of MMI ranged from 27% to 100% (mean = 81.1 +/- 11.4%). The mean serum elimination half-life was 6.6 +/- 2.0 h, with a wide range of values (1.9 h to 15.1 h). After repeat i.v. administration of MMI following 2 weeks of oral administration of the drug, no significant difference was found between mean serum concentrations after single-dose and multiple-dose administration. No significant change in serum elimination half-life or total body clearance was found after multiple-dose administration of MMI. Two cats with the longest half-lives (9.9 h and 15.1 h), however, did exhibit markedly shorter t1/2 values (3.5 h and 3.3 h, respectively) after multiple-dose administration. Values for central and steady state volumes of distribution also decreased after multiple-dose administration, possibly indicating saturation of thyroid uptake of MMI with chronic administration. These results indicate that MMI has good oral bioavailability and has a longer mean serum elimination half-life than propylthiouracil, the other anti-thyroid drug that has been evaluated in cats. Although no significant change in mean values occurred after multiple-dose administration of MMI, drug-induced acceleration of metabolism may occur in some cats after long-term MMI administration.
Absorption↗
The use of antithyroid drugs in the medical management of feline hyperthyroidism.
Antithyroid drugs are widely used in human medicine for the medical management of Graves' disease. Because patients with Graves' disease may undergo spontaneous remission, antithyroid drugs are preferred for long-term therapy because they do not permanently affect thyroid function. Hyperthyroidism in cats is somewhat different, in that spontaneous remission has not been reported and therefore ablative treatment (surgery or radioiodine) is often preferred. However, antithyroid drugs are essential for preoperative stabilization of cats with hyperthyroidism and often are used for long-term management of certain cases. This chapter will review the various drugs available for the medical management of hyperthyroidism, their mechanisms of action, indications for use, and adverse side effects.
Animals↗