Differential pulse polarographic investigation of micafungin and anidulafungin using a dropping mercury electrode.

The electrochemical behavior of the echinocandin antifungals anidulafungin (AF) and micafungin (MF) has been investigated by differential pulse polarography (DPP). The measurements were carried out in a supporting electrolyte solution consisting of Britton-Robinson buffer and methanol at various substance concentrations and pH values. An amperometric cell with a three electrode system consisting of a dropping mercury electrode (DME) as working electrode, an auxiliary platinum electrode and an Ag/AgCl reference electrode was used in all experiments. AF was electrochemically reduced at potentials between -1.3 and -1.5 V. MF showed a first reduction peak (a) between -1.0 and -1.4 V and a second peak (b) between -1.5 and -1.8 V. A strong pH-dependence was observed, with optimal results at pH 2.0-3.0 for the AF peak, pH 2.0 for the MF peak (a) and pH 5.0 for the MF peak (b). A linear correlation between the concentration and the peak current has been demonstrated for all reduction peaks. MF peak (a) showed a similar behavior to the AF peak regarding shape, peak current and pH-dependence. Therefore, it can be assumed that both reductions are based on the same mechanism, a two-step reduction of the N-acyl group.

Anidulafungin Levels in Breast Milk After Cessation of Treatment: A Case Report.

Background: Anidulafungin has poor oral bioavailability, with hardly any available information on how it affects breast milk, oral absorption, or gastrointestinal side effects in the infant. Case Presentation: A 40-year-old woman who recently gave birth to a healthy infant was treated for a period of 14 days for a Candida glabrata with 100 mg anidulafungin once a day. The department of clinical pharmacy was consulted to provide advice on how long the patient had to wait after ceasing anidulafungin before it was safe to start breastfeeding, with regard to preventing possible side effects of the drug to the infant, such as diarrhea or cholestasis and increase in liver enzyme values. The advice of the hospital pharmacist was pragmatic: to start breastfeeding within 2 days after the medication was discontinued based on half-time. Results: Owing to this lack of information, we measured anidulafungin concentrations in breast milk and found low levels. Conclusion: We concluded that anidulafungin is detectable in breast milk until 32 hours after anidulafungin treatment was stopped, and that no side effects were observed by the infant.

Quantification of anidulafungin and micafungin in human body fluids by high performance-liquid chromatography with UV-detection.

The echinocandins anidulafungin (ANID) and micafungin (MICA) are recommended for treatment of invasive Candida infections. As target-site concentrations of antimicrobial agents are crucial for eradication of pathogens, we established and validated high-performance liquid chromatography-UV detection (HPLC-UV) assays for quantification of ANID and MICA in human plasma, ascites fluid, pleural effusion, and in cerebrospinal fluid (CSF). Sample pre-purification was performed by protein precipitation with acetonitrile followed by solid phase extraction. For both assays, intra- and interday precision, and accuracy fulfilled the requirements for bioanalytical methods issued by the European Medicine Agency (EMA). The lower limit of quantification was 0.01 mg/L for both drugs. At 25 °C, ANID and MICA concentrations declined by up to 70% within 24 h. Concentrations remained stable over 24 h at 4 °C and over four weeks at -80 °C. In conclusion, the developed methods are fit for the assessment of target-site pharmacokinetics of ANID and MICA in clinical studies.