Determination of Blood Concentration of Azole Antifungal Agents
Product overview
In this project, high performance liquid chromatography tandem mass spectrometry is used to determine the plasma concentration in patients to assist in accurate antifungal medication in clinical practice.
I. Why test the blood concentration of fungi?
1.Many and serious adverse reactions
Azoles have a high rate of adverse reactions, and abnormal liver function, rash, hypokalemia, visual abnormalities, hallucinations, and vomiting are common in clinical practice.
2.Large individual variation in plasma concentration
The plasma concentration of azoles varies greatly among individuals due to genetic, liver and kidney diseases, and physiological factors.
1) The pharmacokinetics of voriconazole in human body is nonlinear. With the increase of dose, the plasma concentration increases significantly, and the minimum concentration has little correlation with the dose.
2) CYP2C19 gene polymorphisms have a greater impact on the efficacy and safety of voriconazole. Asian races had a much higher proportion of CYP2C19 poor metabolizers than Caucasians and African races.
3) Physiological factors affect, there are gender, age, weight and other individual differences.
4) Pathological factors, such as abnormal liver and kidney function.
3. Plasma concentration correlates with efficacy
Too high plasma concentration predisposes to adverse reactions, and too low has no antifungal effect. Drug concentration monitoring can increase the effectiveness and safety of antifungal infection treatment. For example, the minimum plasma concentration target range of voriconazole is 0.5 – 5 mg/L, and the effective concentration threshold of posaconazole for preventing invasive fungal infections is 0.47 mg/L.
II. Who should monitor plasma concentrations of voriconazole?
1. liver dysfunction;
2. patients with drug combination affecting the pharmacokinetics of azole antifungal drugs;
3. Patients with CYP2C19 gene mutation;
4. patients with adverse drug events or suboptimal response to voriconazole;
5. life-threatening patients with severe fungal infections.
III. How to select the time of blood collection?
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Drug
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Test value
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Blood sampling time
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Voriconazole
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Minimum concentration
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Within half an hour before dosing after Day 3 of dosing
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Posaconazole
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Minimum concentration
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Within half an hour before drug administration in the morning after Day
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Itraconazole
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Minimum concentration
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Within half an hour before dosing after Day 7 of iv dosing
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Fluconazole
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AUC
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Blood samples will be collected at 1, 4 and 24 (before the next dose) hours after administration on Day 7
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