Hepatic uptake of the novel antifungal agent caspofungin.
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Sandhu P, Lee W, Xu X, Leake BF, Yamazaki M, Stone JA, Lin JH, Pearson PG, Kim RB
Hepatic uptake of the novel antifungal agent caspofungin.
Drug Metab Dispos. 2005 May;33(5):676-82. Epub 2005 Feb 16.
- PubMed ID
- 15716364 [ View in PubMed]
- Abstract
Caspofungin (CANCIDAS, a registered trademark of Merck & Co., Inc.) is a novel echinocandin antifungal agent used in the treatment of esophageal and invasive candidiases, invasive aspergillosis, and neutropenia. Available data suggest that the 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. To identify a relevant hepatic uptake transporter, we developed novel Tet-on 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.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Caspofungin P-glycoprotein 1 Protein Humans UnknownInhibitorDetails Caspofungin Solute carrier family 22 member 6 Protein Humans UnknownInhibitorDetails Caspofungin Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownInhibitorDetails Caspofungin Solute carrier organic anion transporter family member 1B3 Protein Humans UnknownSubstrateDetails Indomethacin Solute carrier family 22 member 6 Protein Humans UnknownSubstrateInhibitorDetails Lovastatin Solute carrier organic anion transporter family member 1B1 Protein Humans UnknownSubstrateInhibitorDetails Quinidine Solute carrier family 22 member 1 Protein Humans UnknownInhibitorDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareCaspofunginRifampicin The serum concentration of Caspofungin can be decreased when it is combined with Rifampicin.