HPLC measurement, blood distribution, and pharmacokinetics of oral clotrimazole, potentially useful antisickling agent.
Journal Article (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
- England