HPLC measurement, blood distribution, and pharmacokinetics of oral clotrimazole, potentially useful antisickling agent.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Rifai, N; Sakamoto, M; Law, T; Platt, O; Mikati, M; Armsby, CC; Brugnara, C

Published Date

  • March 1995

Published In

Volume / Issue

  • 41 / 3

Start / End Page

  • 387 - 391

PubMed ID

  • 7882513

International Standard Serial Number (ISSN)

  • 0009-9147

Language

  • eng

Conference Location

  • United States