Clinical efficacy and pharmacokinetics of levothyroxine suppository in patients with hypothyroidism
Open accessAbstract
This study aimed to elucidate the clinical efficacy and pharmacokinetics of levothyroxine (LT4) suppository, thus, we examined the pharmacokinetics of thyroxine (T4) after the administration of the suppository in thyroidectomized rats and examined dose and the levels of free T4 (FT4) in patients with hypothyroidism receiving suppositories. Thyroidectomized rats were administered with LT4 solution and LT4 suppository (30 µg/kg), and plasma T4 concentrations were measured using LC/MS. The AUC0-168 of T4 after rectal administration of the LT4 suppository was 64% lower than these values after oral administration. To evaluate clinical effect of LT4 suppository, we enrolled 6 Japanese patients with hypothyroidism (2 men and 4 women; age, 68.2±13.5 years) who were administered LT4 suppository at Kameda Medical Center from 2007 to 2013 in this case series. The FT4 level during the administration of suppositories was significantly lower than that during the administration of tablets (0.657±0.183 ng/dL vs. 1.25±0.51 ng/dL, p=0.034). The FT4/dose ratio for the suppository was significantly 44% lower than that for the tablet (p=0.020). In conclusion, although the bioavailability of LT4 is lower after administration of the suppository than after the oral formulation, it was suggested that T4 levels can be maintained in patients with hypothyroidism by administering LT4 suppositories at a dose 1.8 times higher than that of the tablet. Thus, the administration of LT4 suppository can be an alternative for treatment with oral medication in clinical practice.
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Expression levels of thyroid hormone transporters differ between the small intestine and the rectum.
“On the other hand, the expression levels of TH transporters differ between the small intestine and the rectum, which, in part, may explain the differences in the bioavailability of T4 after oral and rectal administration (261).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [261]
Differences in thyroid hormone transporter expression between the small intestine and rectum may in part explain differences in T4 bioavailability after oral and rectal administration.
“On the other hand, the expression levels of TH transporters differ between the small intestine and the rectum, which, in part, may explain the differences in the bioavailability of T4 after oral and rectal administration (261).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [261]
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- Authors
- Kashiwagura, Y., Uchida, S., Tanaka, S., Watanabe, H., Masuzawa, M., Sasaki, T., & Namiki, N.
- Affiliations
- Shizuoka University (JP)
- Hamamatsu University School of Medicine (JP)
- Kameda Medical Center (JP)
- Venue
- Biological and Pharmaceutical Bulletin
- Publisher
- Pharmaceutical Society of Japan
- Published
- 2014
- Volume
- 37
- Issue
- 4
- Pages
- 666-670
- ISSN
- 0918-6158 (ISSN-L)
- 1347-5215
- OpenAlex
- W2015442325
- Cited by
- 18
- References
- 12
- Citations by year
- 2026: 3 · 2025: 2 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Locations
- Biological and Pharmaceutical Bulletin (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- levothyroxine, suppositories, hypothyroidism, pharmacokinetics, bioavailability, free thyroxine, thyroidectomy, rectal administration, dose adjustment
- MeSH terms
- Administration, Oral, Aged, Aged, 80 and over, Animals, Biological Availability, Female, Humans, Hypothyroidism, Male, Middle Aged, Solutions, Suppositories, Tablets, Thyrotropin, Thyroxine, Triiodothyronine, Rats
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