Effect of soy extract administration on losartan pharmacokinetics in healthy female volunteers.
BACKGROUND
osartan is metabolized by CYP2C9 and CYP3A4 to an active metabolite, E-3174, which has greater antihypertensive activity than the parent compound. Soy extract has been shown to be an activator of CYP2C9 and CYP3A4 in vitro. Coadministration of soy extract and losartan may therefore alter the pharmacokinetics of losartan and E-3174.


OBJECTIVE
To determine whether, when losartan was used in combination with soy extract, a significant pharmacokinetic interaction would be observed in healthy female volunteers.


METHODS
Eighteen healthy Chinese female volunteers were recruited. In an open-label, 2-phase study, losartan 50 mg was given to each subject, with and without soy extract. Plasma concentrations of losartan and E-3174 were determined by liquid chromatography-tandem mass spectrometry for 12 and 24 hours, respectively. On day 8 through day 21 of the study, following a 7-day washout period, each subject consumed two 1000-mg Genistein Soy Complex tablets orally after meals, twice daily, for 14 days. On day 22, all volunteers received losartan 50 mg and blood samples were collected again.


RESULTS
All subjects completed the study, without adverse drug effects. Over the 14-day pretreatment period, soy extract did not significantly influence the pharmacokinetics of losartan or E-3174. The ratio of the area under the curve of the drug and metabolite after losartan administration, with and without soy extract ingestion, was 0.21 +/- 0.05 and 0.23 +/- 0.05 (mean +/- SD), respectively. The difference was not statistically significant (p = 0.22).


CONCLUSIONS
Our data indicate that a significant interaction between soy extract and losartan is unlikely to occur in females.
Wang
Guo
G
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.
Xiao
Chang-Qiong
CQ
Li
Zhi
Z
Guo
Dong
D
Chen
Yao
Y
Fan
Lan
L
Qian
Rong-Hua
RH
Peng
Xiu-Juan
XJ
Hu
Dong-Li
DL
Zhou
Hong-Hao
HH
D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001189:Aryl Hydrocarbon Hydroxylases / Q000187:drug effects / Q000378:metabolism; D002681:China; D002853:Chromatography, Liquid; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics; D019808:Losartan / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D013777:Tetrazoles / Q000493:pharmacokinetics; D013997:Time Factors; D055815:Young Adult
D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D010936:Plant Extracts; D013777:Tetrazoles; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C066026:losartan carboxylic acid; D019808:Losartan