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Joiner et al
The range of pH measurements for all samples and comparators were 8.4 to 8.7 and did not deviate from this at any time
point throughout the 2-hour observation period.
Current literature and clinical practice recommend a NS or
D5W vehicle for intravenously delivered micafungin. However,
this study was designed to determine physical compatibility of
micafungin in a basic vehicle to alkalinize the urine in patients
taking concomitant HDMTX. The chemical stability of micafungin in an alkaline pH aqueous solution has been reported in
2 forced degradation studies as part of the validation for stability indicating assays. Zhu et al10 reported a loss of 25.1% of a
2.5 mg/mL solution of micafungin in a 0.1 M NaOH solution
(pH = 13) at room temperature after 1 hour. Briot et al11 measured a 27% chemical degradation of a 2 mg/mL solution of
micafungin also in a 0.1 M NaOH solution (pH = 13) after 30
minutes at room temperature. While both of these studies report
significant chemical instability of micafungin in an alkaline
solution, it should be noted that the pH was much higher (13 vs
8.4) and the time the micafungin is mixed with alkaline solution was much longer than what would occur in a clinical setting. Based on the flow rates and size and length of typical IV
tubing used, the residence time of micafungin in our vehicles
prior to entering the patient would not exceed 5 minutes. While
this study did not address the chemical stability of micafungin
in an alkaline solution, no significant loss of potency would be
expected under the reported clinical parameters of use.
All 3 combinations of micafungin in various sodium bicarbonate-containing vehicles were deemed compatible physically
based on our predefined criteria. Traditionally, Y-site compatibility studies for peripheral lines are conducted using a 1:1 ratio
of the 2 solutions being evaluated.12 To accurately simulate
administration of micafungin with the various vehicles used in
clinical practice, a volume ratio of the vehicle-drug relationship
was determined. The basis for the 3:1 ratio of vehicle to micafungin is derived from the differential flow rates of the 2 solutions flowing into the Y-site. In our institution, the flow rate for
the vehicle solutions is typically 125 mL/m2/h while micafungin
is 50 to 100 mL/h. Based on the variable body surface area of
the patients and the flow rate of micafungin, a 3:1 ratio was
deemed to be appropriate. At any given time, the makeup of the
combined medication solution will favor the vehicle because
they typically have a greater flow rate than micafungin.
However, the large difference in flow rates between micafungin
and the vehicles mandated a change in the volume ratio.
The observed physical compatibility of the combinations
evaluated in this work are likely influenced from the 3:1 ratio
used in the study which results in a larger dilution effect on the
micafungin as compared with a traditional 1:1 ratio evaluation. Physical compatibility of a 1:1 ratio of the vehicles evaluated in this study should not be extrapolated from these results.

Conclusion
The results of this study demonstrate the Y-site/CVC physical
compatibility for up to 2 hour of micafungin sodium (1.5 mg/

mL in NS) with different concentrations of sodium bicarbonate
hydration fluids administered to patients receiving HDMTX.
These data support options for modified IV Y-site/CVC dosing
modalities for these patients and should be useful in reducing
the requirement of venous access or in cases of limited access.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

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