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Biomedical subjects

L A Trepanier

Publications and source records attributed to L A Trepanier.

13 recordsLinked to original sources
PubMed1997

Cytosolic arylamine N-acetyltransferase (NAT) deficiency in the dog and other canids due to an absence of NAT genes.

The purpose of this study was to determine the molecular basis in the dog for an unusual and absolute deficiency in the activity of cytosolic N-acetyltransferase (NAT), an enzyme important for the metabolism of arylamine and hydrazine compounds. NAT activity towards two NAT substrates, p-aminobenzoic acid and sulfamethazine, was undetectable in dog liver cytosol, despite substrate concentrations ranging from 10 microM to 4 mM and a wide range of incubation times. Similarly, no protein immunoreactive to NAT antibody was evident on western blot analysis of canine liver cytosol. Southern blot analysis of genomic DNA from a total of twenty-five purebred and mixed bred dogs, and eight wild canids, probed with a full-length human NAT2 cDNA, suggested an absence of NAT sequences in all canids. Polymerase chain reaction amplification of genomic DNA using degenerate primers designed to mammalian NAT1 and NAT2 consensus sequences generated products of the expected size in human, mouse, rabbit, and cat DNA, but no NAT products in any dog or wild canids. These results support the conclusion that cytosolic NAT deficiency in the domestic dog is due to a complete absence of NAT genes, and that this defect is shared by other canids.

4-Aminobenzoic Acid↗
PubMed1996

Bromide toxicosis secondary to renal insufficiency in an epileptic dog.

Bromide toxicosis was diagnosed in an 8-year-old Labrador Retriever that had been treated for epilepsy with potassium bromide, at a dosage of 29 mg/kg of body weight/d. Clinical signs included hind limb weakness, ataxia, and disorientation. Renal insufficiency, diagnosed by determination of endogenous creatinine clearance, was believed to be responsible for the development of bromide toxicosis in this dog. Diuresis with physiologic saline solution and discontinuation of bromide and phenobarbital treatment resulted in rapid resolution of abnormal neurologic signs; however, serum bromide concentrations decreased dramatically during diuresis and seizures recurred. Although saline diuresis has been recommended for the treatment of bromide intoxication in human beings, more conservative measures, such as discontinuation of bromide and short-term fluid administration, may be more appropriate for epileptic dogs.

Animals↗
PubMed1996

High dietary chloride content associated with loss of therapeutic serum bromide concentrations in an epileptic dog.

Bromide treatment was successful in controlling seizures in an 11-year-old Dachshund with epilepsy and presumptive phenobarbital-associated hepatopathy. Because bromide does not induce liver enzyme activity and does not seem to be hepatotoxic, it can be used to control seizures in dogs with concurrent epilepsy and hepatic disease. In this dog, institution of a special calculolytic diet with high chloride content was associated with a decrease in serum bromide concentrations and the recurrence of seizures. High chloride intake increases the elimination of bromide in dogs, leading to higher dosage requirements for bromide in dogs fed high-chloride diets.

Animals↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1992

Bromism.

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Animals↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗