Clinical Evaluation of a Novel Liquid Formulation of L‐Thyroxine for Once Daily Treatment of Dogs with Hypothyroidism

Abstract

Background: A liquid solution of levothyroxine (L-T4) is available for treatment of canine hypothyroidism. Hypothesis: Once daily oral administration of a liquid L-T4 solution is effective and safe for controlling hypothyroidism in dogs.Animals: Thirty-five dogs with naturally occurring hypothyroidism. Methods: Dogs received L-T4 solution PO once daily at a starting dosage of 20 mg/kg body weight (BW). The dose was adjusted every 4 weeks, based on clinical signs and peak serum total T4 (tT4) concentrations. Target peak serum tT4 and thyroid stimulating hormone (TSH) concentrations, 4-6 hours posttreatment, were 35-95 nmol/L and o 0.68 ng/mL, respectively. Dogs were followed for up to 22 weeks after establishment of the maintenance dose.Results: Clinical signs of hypothyroidism improved or resolved in 91% of dogs after 4 weeks of L-T4 treatment at 20 mg/kg once daily. The maintenance dose was established in 76, 94, and 100% of dogs after 4, 8, and 12 weeks of treatment, respectively. This was 20 mg L-T4/kg BW for 79% of the dogs, 30 mg/kg BW for 15%, and 10-15 mg/kg BW in the remaining 6%, once daily. Thereafter, median peak tT4 and TSH concentrations were 51 nmol/L and 0.18 ng/mL, respectively, and remained stable during the 22-week follow-up; clinical signs did not recur.Conclusions and Clinical Importance: All of the hypothyroid dogs had rapid clinical and hormonal responses to supplementation with the PO-administered L-T4 solution. The starting dosage of 20 mg L-T4/kg BW once daily was suitable for 79% of dogs.

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

“…The pharmacokinetic profiles of tT 4 in hypothyroid dogs in this study provide pharmacological evidence, in addition to clinical data published earlier, 3 that once daily dosing of L-T 4 solution is an appropriate treatment for spontaneous primary hypothyroidism in dogs. This dosing schedule could improve treatment compliance and thus decrease apparent treatment failure.…”

“…This finding is in agreement with clinical observations that this L-T 4 solution at a dosage of 20 lg/kg once daily, was effective in most hypothyroid dogs. 3 In that study, clinical signs of hypothyroidism improved or resolved in 91% of the dogs after 4 weeks of treatment at this dosage and this dosage was suitable for once daily maintenance in 79%, with 30 lg/kg required for 15%, and 10-15 lg/kg for 6%. The peak tT 4 concentration (4-6 hours after dosing) of 51 nmol/L (median) reported in that clinical efficacy study was very close to our results (46 AE 14.1 nmol/L at 4 hours, 46 AE 12.5 nmol/L at 6 hours).…”

“…Once-daily L-T 4 supplementation facilitates compliance and was shown to appropriately control hypothyroidism in most dogs. 3,4 After initial treatment of hypothyroidism for 4-8 weeks, the dosage regimen should be adjusted individually, based on changes in clinical signs and tT 4 and thyroid-stimulating hormone (TSH) concentrations. 1,5,6 Optimal dosage and frequency of supplementation vary because of variability in L-T 4 absorption and biological half-life in dogs.…”

Hypothyroidism

“…The plasma half-life of L-T 4 sodium in dogs ranges from 9 to 14 hours and depends, in part, on the dosage and frequency of administration, with higher dosages and more frequent administration associated with a shorter half-life of L-T 4 sodium (Nachreiner et al, 1993;Le Traon, 2007). Most studies have shown that the majority of dogs have a good clinical response to treatment with once daily L-T 4 sodium; however dose adjustments are required in 20% to 50% of dogs started on once a day therapy (Le Traon et al, 2009;Dixon et al, 2002). At this dosage, mean time to peak serum T 4 concentration was 3.8 ± 2.0 hours after L-T 4 sodium administration.…”

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

“…The investigators chose to administer levothyroxine once daily based on the resolution of clinical abnormalities of hypothyroidism in dogs supplemented in a similar manner. 20,21 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.…”