Hepatic uptake of the novel antifungal agent caspofungin.
Author:
Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB.
Date: 3 March 2005
Abstract:
Caspofungin (CANCIDAS(TM))(2) is a novel echinocandin antifungal agent used in the treatment of esophageal and invasive candidiases, invasive aspergillosis and neutropenia. Available data suggest liver is a key organ responsible for caspofungin elimination in rodents and humans. Caspofungin is primarily eliminated by metabolic transformation, however, the rate of metabolism is slow. Accordingly, it was hypothesized that drug uptake transporters expressed on the basolateral domain of hepatocytes could significantly influence the extent of caspofungin uptake and subsequent elimination. In this study, experiments ranging from perfused rat livers to heterologous expression of individual hepatic uptake transporters were utilized to identify the transporter(s) responsible for the observed liver-specific uptake of this compound. Data from perfused rat liver studies were consistent with the presence of carrier-mediated caspofungin hepatic uptake, although this process appeared to be slow. In order to identify a relevant hepatic uptake transporter, we developed novel Tet-on(TM) HeLa cells expressing OATP1B1 (OATP-C, SLC21A6) and OATP1B3 (OATP8, SLC21A8), whose target gene can be overexpressed by the addition of doxycycline. A modest but statistically significant uptake of caspofungin was observed in cells overexpressing OATP1B1, but not OATP1B3. Taken together, these findings suggest that OATP1B1 mediated hepatic uptake may contribute to the overall elimination of this drug from the body.
Download the full article (Disclaimer)
This manuscript library of ~16,000 articles (1729-2024) related to Aspergillus and aspergillosis is intended for individual study only, and is provided as contribution to global understanding of the topic. Please refer to the publisher’s guidance about any other usage.