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 Ca2+-activated K+ channel and to thereby prevent Kloss and cellular dehydration of sickled erythrocytes. This evidence s uggests that oral CLT may be a useful new therapy for sickle cell dise ase. 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 mu mol/L ; the detection limit was 0.1 mu mol/L, analytical recovery 97.7%, and run-to-run imprecision (CV) <4.7%. In unaffected subjects, CLT concen tration 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 thera peutic monitoring of CLT concentrations.