HPLC Measurement, Bbod Distribution, and Pharmacokinetics of Oral Clotrimazole, Potentially Useful Antisickling Agent

Clotrimazole (CLI) has recently been shown to be a potent and specific inhibitor of the Ca2-activated K channel and to thereby prevent K loss and cellular dehydration of sickled erythrocytes. This evidence sug-gests that oral CLI 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 moVL; the detection limit was 0.1 moVL, 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 hyper