HPLC measurement, blood distribution, and pharmacokinetics of oral clotrimazole, potentially useful antisickling agent.
Clotrimazole (CLT) has recently been shown to be a potent and specific inhibitor of the Ca(2+)-activated K+ channel and to thereby prevent K+ loss and cellular dehydration of sickled erythrocytes. This evidence suggests that oral CLT may be a useful new therapy for sickle cell disease. Here, we describe the development of an HPLC assay to measure CLT, a method we used to study the pharmacokinetics and transport of CLT in normal volunteers. The assay's linear range extended to 10 mumol/L; the detection limit was 0.1 mumol/L, analytical recovery 97.7%, and run-to-run imprecision (CV) < 4.7%. In unaffected subjects, CLT concentration peaked within 6 h of oral administration and returned to close to baseline by 24 h. High-density lipoproteins appear to be the main carriers of this drug in both normo- and hypertriglyceridemic plasma. We conclude that the method described here is ideally suited for therapeutic monitoring of CLT concentrations.
Duke Scholars
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Related Subject Headings
- Triglycerides
- Sensitivity and Specificity
- Lipoproteins, LDL
- Lipoproteins, HDL
- Kinetics
- Humans
- General Clinical Medicine
- Clotrimazole
- Chromatography, High Pressure Liquid
- Biological Transport
Citation
Published In
ISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Triglycerides
- Sensitivity and Specificity
- Lipoproteins, LDL
- Lipoproteins, HDL
- Kinetics
- Humans
- General Clinical Medicine
- Clotrimazole
- Chromatography, High Pressure Liquid
- Biological Transport