Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model

The use of radiopharmaceuticals for infection detection has gained increasing attention for their application in nuclear medicine. The administration of [99mTc]Tc-ketoconazole may altere pharmacological aspects including interaction data with some antifungals especially ketoconazole as a common drug...

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Autores principales:	Ahmad Kurniawan, Rizky Juwita Sugiharti, Iim Halimah, Iswahyudi Iswahyudi, Maula Eka Sriyani
Formato:	article
Lenguaje:	EN
Publicado:	Universitas Gadjah Mada 2021
Materias:	drug interaction, radiopharmaceuticals, [99mtc]tc-ketoconazole, candidiasis, ketoconazole. Pharmacy and materia medica RS1-441
Acceso en línea:	https://doaj.org/article/2f8bf0fb8092403eb3c6a7b3a6448899
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spelling	oai:doaj.org-article:2f8bf0fb8092403eb3c6a7b3a64488992021-11-15T06:08:47ZDrug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model2338-94272338-948610.22146/ijp.899https://doaj.org/article/2f8bf0fb8092403eb3c6a7b3a64488992021-03-01T00:00:00Zhttps://jurnal.ugm.ac.id/v3/IJP/article/view/899https://doaj.org/toc/2338-9427https://doaj.org/toc/2338-9486The use of radiopharmaceuticals for infection detection has gained increasing attention for their application in nuclear medicine. The administration of [99mTc]Tc-ketoconazole may altere pharmacological aspects including interaction data with some antifungals especially ketoconazole as a common drug for candidiasis treatment. The current study investigated the ex vivo biodistribution and pharmacokinetic interaction of [99mTc]Tc-ketoconazole after ketoconazole administration in BALB/c mice. In this research,The [99mTc]Tc-ketoconazole was prepared with radiochemical purity 94.59% (n=3). The ex vivo biodistribution uptake in infected muscle as a target organ showed 0.16±0.13%ID/g for control, 0.17±0.12 for 1 h, and 0.05±0.04 for 3 h after ketoconazole administration. The Target/Non-Target (T/NT) ratio between infected muscle compared with normal muscle showed 1.19±0.13 for the control group, 2.56±1.71 for 1 h and 0.86±0.67 for 3 h. The ex vivo biodistribution also showed high radioactivity uptake on the liver, lung, spleen and kidney. Pharmacokinetics analysis using PKSolver showed [99mTc]Tc-ketoconazole half-life elimination (t1/2 beta) for the therapy group showed shorter elimination time 13.78±4.77 h compared with the control group 44.77±2.74 h after ketoconazole administration. Pharmacokinetics parameter change also occurred on the area under the curve of therapy group (AUC 0-inf) that is 26.10±18.97 %ID/g*h and maximum concentration (Cmax) 13.05±9.48 %ID/g which was related with radiopharmaceutical absorption rate. This study proves that based on biodistribution and pharmacokinetics evaluation, the [99mTc]Tc-ketoconazole application was recommended at 1 h post ketoconazole administration.Ahmad KurniawanRizky Juwita SugihartiIim HalimahIswahyudi IswahyudiMaula Eka SriyaniUniversitas Gadjah Madaarticledrug interaction, radiopharmaceuticals, [99mtc]tc-ketoconazole, candidiasis, ketoconazole.Pharmacy and materia medicaRS1-441ENIndonesian Journal of Pharmacy, Pp 106-113 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	drug interaction, radiopharmaceuticals, [99mtc]tc-ketoconazole, candidiasis, ketoconazole. Pharmacy and materia medica RS1-441
spellingShingle	drug interaction, radiopharmaceuticals, [99mtc]tc-ketoconazole, candidiasis, ketoconazole. Pharmacy and materia medica RS1-441 Ahmad Kurniawan Rizky Juwita Sugiharti Iim Halimah Iswahyudi Iswahyudi Maula Eka Sriyani Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model
description	The use of radiopharmaceuticals for infection detection has gained increasing attention for their application in nuclear medicine. The administration of [99mTc]Tc-ketoconazole may altere pharmacological aspects including interaction data with some antifungals especially ketoconazole as a common drug for candidiasis treatment. The current study investigated the ex vivo biodistribution and pharmacokinetic interaction of [99mTc]Tc-ketoconazole after ketoconazole administration in BALB/c mice. In this research,The [99mTc]Tc-ketoconazole was prepared with radiochemical purity 94.59% (n=3). The ex vivo biodistribution uptake in infected muscle as a target organ showed 0.16±0.13%ID/g for control, 0.17±0.12 for 1 h, and 0.05±0.04 for 3 h after ketoconazole administration. The Target/Non-Target (T/NT) ratio between infected muscle compared with normal muscle showed 1.19±0.13 for the control group, 2.56±1.71 for 1 h and 0.86±0.67 for 3 h. The ex vivo biodistribution also showed high radioactivity uptake on the liver, lung, spleen and kidney. Pharmacokinetics analysis using PKSolver showed [99mTc]Tc-ketoconazole half-life elimination (t1/2 beta) for the therapy group showed shorter elimination time 13.78±4.77 h compared with the control group 44.77±2.74 h after ketoconazole administration. Pharmacokinetics parameter change also occurred on the area under the curve of therapy group (AUC 0-inf) that is 26.10±18.97 %ID/g*h and maximum concentration (Cmax) 13.05±9.48 %ID/g which was related with radiopharmaceutical absorption rate. This study proves that based on biodistribution and pharmacokinetics evaluation, the [99mTc]Tc-ketoconazole application was recommended at 1 h post ketoconazole administration.
format	article
author	Ahmad Kurniawan Rizky Juwita Sugiharti Iim Halimah Iswahyudi Iswahyudi Maula Eka Sriyani
author_facet	Ahmad Kurniawan Rizky Juwita Sugiharti Iim Halimah Iswahyudi Iswahyudi Maula Eka Sriyani
author_sort	Ahmad Kurniawan
title	Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model
title_short	Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model
title_full	Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model
title_fullStr	Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model
title_full_unstemmed	Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model
title_sort	drug interaction evaluation of [99mtc]tc-ketoconazole uptake with ketoconazole administration in candidiasis mice model
publisher	Universitas Gadjah Mada
publishDate	2021
url	https://doaj.org/article/2f8bf0fb8092403eb3c6a7b3a6448899
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Drug interaction evaluation of [99mTc]Tc-ketoconazole uptake with ketoconazole administration in Candidiasis mice model

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