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Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats

Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted p...

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Autores principales: Jeong, Seung-Hyun, Jang, Ji-Hun, Lee, Yong-Bok
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559546/
https://www.ncbi.nlm.nih.gov/pubmed/32887301
http://dx.doi.org/10.3390/ph13090231
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author Jeong, Seung-Hyun
Jang, Ji-Hun
Lee, Yong-Bok
author_facet Jeong, Seung-Hyun
Jang, Ji-Hun
Lee, Yong-Bok
author_sort Jeong, Seung-Hyun
collection PubMed
description Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes.
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spelling pubmed-75595462020-10-26 Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats Jeong, Seung-Hyun Jang, Ji-Hun Lee, Yong-Bok Pharmaceuticals (Basel) Article Topotecan is actively used in clinic, with its primary use being in treatment of various types of cancer. The approved administration routes are oral and intravenous. The purpose of this study was to investigate and identify pharmacokinetic profiles of different administration routes. We conducted pharmacokinetic studies on three different routes of administration in rats. Five rats in each group received a single dose of 4 mg/kg of topotecan hydrochloride intravenously, orally, or subcutaneously, and the concentrations of lactone and total forms of the drug in plasma, urine, and feces were quantified. Various pharmacokinetic parameters were compared statistically. Plasma concentrations of both the lactone and total forms at elimination phase following subcutaneous administration, were two times higher than was seen with oral administration and 10 times higher than with intravenous administration. Subcutaneous administration of topotecan showed pharmacokinetic profiles similar to sustained release. In addition, subcutaneous administration showed bioavailability from 88.05% (for lactone form) to 99.75% (for total form), and these values were four–five times greater than those of oral administration. The results of this non-clinical study will not only provide greater understanding of the in vivo pharmacokinetics of topotecan, but also be useful for development of additional formulations and/or administration routes. MDPI 2020-09-02 /pmc/articles/PMC7559546/ /pubmed/32887301 http://dx.doi.org/10.3390/ph13090231 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jeong, Seung-Hyun
Jang, Ji-Hun
Lee, Yong-Bok
Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats
title Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats
title_full Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats
title_fullStr Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats
title_full_unstemmed Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats
title_short Pharmacokinetic Comparison of Three Different Administration Routes for Topotecan Hydrochloride in Rats
title_sort pharmacokinetic comparison of three different administration routes for topotecan hydrochloride in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559546/
https://www.ncbi.nlm.nih.gov/pubmed/32887301
http://dx.doi.org/10.3390/ph13090231
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