ArticleDrug metabolism and disposition: the biological fate of chemicals2010
In vitro investigation of the hepatobiliary disposition mechanisms of the antifungal agent micafungin in humans and rats.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 59 citations in OpenAlex.
- Fractal geometry and the pharmacometrics of micafungin in overweight, obese, and extremely obese people.Antimicrobial agents and chemotherapy · 2011Trial
- Systematic analysis of echinocandin-associated adverse reactions using the FAERS database: identification of unique DRESS and resistance signals.Frontiers in medicine · 2026Article
- Multitasking NaBiomedicines · 2022Review
- Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes.European journal of drug metabolism and pharmacokinetics · 2019Review
- Effect of Cryopreservation on Enzyme and Transporter Activities in Suspended and Sandwich Cultured Rat Hepatocytes.The AAPS journal · 2018Article
- Sodium taurocholate cotransporting polypeptide (NTCP) deficiency: Identification of a novelOncotarget · 2017Article
- Pharmacokinetics and Safety of Micafungin in Infants Supported With Extracorporeal Membrane Oxygenation.The Pediatric infectious disease journal · 2016Article
- Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury.Journal of pharmaceutical sciences · 2016Review
- Hepatitis B Virus and Hepatitis D Virus Entry, Species Specificity, and Tissue Tropism.Cold Spring Harbor perspectives in medicine · 2015Review
- Quantitative NTCP pharmacophore and lack of association between DILI and NTCP Inhibition.European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2015Article
- A substrate pharmacophore for the human sodium taurocholate co-transporting polypeptide.International journal of pharmaceutics · 2015Article
- Tacrine sinusoidal uptake and biliary excretion in sandwich-cultured primary rat hepatocytes.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2014Article
- Sodium-dependent bile salt transporters of the SLC10A transporter family: more than solute transporters.Pflugers Archiv : European journal of physiology · 2014Review
- Development and validation of a stability-indicating high performance liquid chromatographic (HPLC) method for the determination of related substances of micafungin sodium in drug substances.International journal of molecular sciences · 2013Article
- Interaction between HIV protease inhibitors (PIs) and hepatic transporters in sandwich cultured human hepatocytes: implication for PI-based DDIs.Biopharmaceutics & drug disposition · 2013Article
- Structure-activity relationship for FDA approved drugs as inhibitors of the human sodium taurocholate cotransporting polypeptide (NTCP).Molecular pharmaceutics · 2013Article
- Nuclear-receptor-mediated regulation of drug- and bile-acid-transporter proteins in gut and liver.Drug metabolism reviews · 2013Review
- Has the era of individualised medicine arrived for antifungals? A review of antifungal pharmacogenomics.Bone marrow transplantation · 2012Review
- Higher clearance of micafungin in neonates compared with adults: role of age-dependent micafungin serum binding.Biopharmaceutics & drug disposition · 2011Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The purpose of the present study was to elucidate the transport mechanisms responsible for elimination of micafungin, a new semisynthetic echinocandin antifungal agent, which is predominantly cleared by biliary excretion in humans and rats. In vitro studies using sandwich-cultured rat and human hepatocytes were conducted. Micafungin uptake occurred primarily (∼75%) by transporter-mediated mechanisms in rat and human. Micafungin uptake into hepatocytes was inhibited by taurocholate (K(i) = 61 μM), Na(+) depletion (45-55% reduced), and 10 μM rifampin (20-25% reduced); these observations support the involvement of Na(+)-taurocholate-cotransporting polypeptide (NTCP/Ntcp) and, to a lesser extent, organic anion-transporting polypeptides in the hepatic uptake of micafungin. The in vitro biliary clearance of micafungin, as measured by the B-CLEAR technique, amounted to 14 and 19 μl/(min · mg protein) in human and rat, respectively. In vitro biliary excretion of micafungin was reduced by 80 and 75% in the presence of the bile salt export pump (BSEP) inhibitors taurocholate (100 μM) and nefazodone (25 μM), respectively. Biliary excretion of micafungin also was reduced in the presence of breast cancer resistance protein inhibitors [N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918) (10 μM) and fumitremorgin C (10 μM)]. In vitro biliary excretion of micafungin was not significantly altered by coincubation with P-glycoprotein or multidrug resistance-associated protein 2 inhibitors. These results suggest that NTCP/Ntcp and BSEP/Bsep are primarily responsible for hepatobiliary disposition of micafungin in human and rat. Interference with hepatic bile acid disposition could be one mechanism underlying hepatotoxicity associated with micafungin in some patients.
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