Pharmacokinetics of Total Thyroxine after Repeated Oral Administration of Levothyroxine Solution and its Clinical Efficacy in Hypothyroid Dogs

Abstract

BackgroundOral levothyroxine (l‐T4) supplementation is commonly used to treat hypothyroid dogs.ObjectivesInvestigate the plasma profile and pharmacokinetics of total thyroxine (tT4) after PO administration of a l‐T4 solution and its clinical efficacy in hypothyroid dogs.AnimalsTen dogs with naturally occurring hypothyroidism.MethodsAfter hypothyroidism diagnosis and supplementation with l‐T4 solution PO q24h at 20 μg/kg BW for minimum 4 weeks, the plasma profile and pharmacokinetics of tT4 were determined over 34 hours and the clinical condition of the dogs was evaluated.ResultsBefore dosing for pharmacokinetic evaluation, mean tT4 concentration was 23 ± 9 nmol/L. l‐T4 was absorbed rapidly (t max, 5 hours), reaching a mean maximal tT4 concentration of 56 ± 11 nmol/L. The apparent terminal half‐life was 11.8 hours. Clinical signs of hypothyroidism improved or resolved in all dogs after 4 weeks of treatment. The dosage of 20 μg/kg PO q24h was judged appropriate in 5 dogs, and 4 dogs required slight increases (9–16%). Twice daily treatment, with a 30% increase in dosage, was necessary for 1 dog.Conclusions and Clinical ImportanceThe pharmacokinetics of l‐T4 in hypothyroid dogs was similar to that reported in healthy euthyroid dogs. Clinical and hormonal responses to l‐T4 solution were rapid in all dogs. The starting dosage of 20 μg/kg PO q24h was suitable for maintenance supplementation in 50% of the dogs, minor dosage modification was required in 4 other dogs, and treatment q12h was required in 1 dog.

Effects of Levothyroxine Administration and Withdrawal on the Hypothalamic‐Pituitary‐Thyroid Axis in Euthyroid Dogs

“…Although once daily dosing results in more fluctuation in serum T 4 concentrations compared to twice daily dosing, the duration of action of T 4 is longer than its plasma half‐life 22, 23, 24, 25, 26. In previous studies of the HPTA, dogs were administered levothyroxine twice daily, making comparisons difficult 6, 14…”

Comparative Pharmacotherapy of Thyroid Diseases in Dogs and Cats--- What Should the Retail Pharmacist Filling Pet Prescriptions Understand?

“…Loss of the extra body weight the dog has gained will follow. These responses can occur over 2 weeks to 2 months, with anticipated resolution of most symptoms in 4 weeks [7]. There are no particular adverse reactions associated with levothyroxine therapy at the recommended dosage levels; however, over dosage will result in the signs of thyrotoxicosis, not dissimilar from people.…”

“…The doses of levothyroxine given to dogs are strikingly higher than those doses typically administered to people, and to an unaccustomed pharmacist, they may appear incorrect. While the dose for an adult person can be 75 to 125 µg a day, a medium-sized (25 kg) dog would begin therapy at ≈500 µg a day (assuming a dose of 20ug/kg/day [8]) and half of dogs may need an upward adjustment of this dose and/ or frequency [7]. Cats rarely develop hypothyroidism; however, in those that do, the levothyroxine dose is one-half the dog dose.…”

“…The lower level of plasma proteinbound T4 leads to T4 half-lives in dogs and cats that is much shorter than in people. The half-life of canine T4 is approximately 12h [7]; feline T4 is approximately 10h, compared with people, who have a T4 half-life of approximately 7 days [5]. In addition, the oral bioavailability of levothyroxine is much lower in dogs than humans [8].…”