Back to Search
Start Over
Gender differences in pharmacokinetics of lumefantrine and its metabolite desbutyl-lumefantrine in rats.
- Source :
-
Biopharmaceutics & drug disposition [Biopharm Drug Dispos] 2012 May; Vol. 33 (4), pp. 229-34. Date of Electronic Publication: 2012 Apr 25. - Publication Year :
- 2012
-
Abstract
- Lumefantrine has been reported to be mainly bio-transformed by cytochrome P450 isozyme 3A4 to desbutyl-lumefantrine (DLF) in human liver microsomes. Since CYP3A is expressed in a sex specific manner in rats, it could be expected that the pharmacokinetics of lumefantrine would be changed in male rats compared with those in female rats. The pharmacokinetics of lumefantrine and its active metabolite DLF were evaluated after intravenous (0.5 mg/kg) and oral (20 mg/kg) administration of lumefantrine to male and female Sprague-Dawley rats. The quantitative bioanalysis was carried out by the liquid chromatography tandem mass spectrometry method. After intravenous and oral administration of lumefantrine the area under the curve (AUC) of lumefantrine was significantly higher in female rats than that in male rats, whereas the AUC of DLF was significantly lower in female rats in comparison with male rats. This lower AUC of DLF in female rats could have been due to reduced metabolism of lumefantrine in female rats. The bioavailability (%F) of lumefantrine was 1.66 times higher in male rats than that in female rats.<br /> (Copyright © 2012 John Wiley & Sons, Ltd.)
- Subjects :
- Administration, Oral
Animals
Antimalarials administration & dosage
Area Under Curve
Biological Availability
Chromatography, Liquid
Dose-Response Relationship, Drug
Ethanolamines administration & dosage
Ethanolamines metabolism
Female
Fluorenes administration & dosage
Fluorenes metabolism
Injections, Intravenous
Lumefantrine
Male
Rats
Rats, Sprague-Dawley
Sex Factors
Tandem Mass Spectrometry
Antimalarials pharmacokinetics
Ethanolamines pharmacokinetics
Fluorenes pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1099-081X
- Volume :
- 33
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biopharmaceutics & drug disposition
- Publication Type :
- Academic Journal
- Accession number :
- 22447530
- Full Text :
- https://doi.org/10.1002/bdd.1786