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

Abstract

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.

Keywords

• drug interaction, radiopharmaceuticals, [99mtc]tc-ketoconazole, candidiasis, ketoconazole.