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DRUG INTERACTIONS

Effect of Soy Extract Administration on Losartan Pharmacokinetics in Healthy Female Volunteers

Assistant Professor, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China

Chang-Qiong Xiao, MD

Pharmacology Student, Assistant Professor, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University

Zhi Li, PhD

Assistant Professor, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University

Dong Guo, PhD

Assistant Professor, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University

Yao Chen, PhD

Assistant Professor, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University

Lan Fan, PhD

Assistant Professor, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University

Rong-Hua Qian, PhD

Assistant Professor, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University

Xiu-Juan Peng, MD

Pharmacology Student, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University

Dong-Li Hu, MD

Pharmacology Student, Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University

Hong-Hao Zhou, MD

Professor, Director, Pharmacogenetics Research Institute, Central South University

Reprints: Dr. Zhou, Pharmacogenetics Research Institute, Central South University, 110 Xiang Ya Rd., Changsha, Hunan 410078, China, 4805379, fax 86 731 2354476, hhzhou2003{at}163.com

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.

Key Words: interaction, isoflavone, losartan, pharmacokinetics, soy extract

Published Online, May 19, 2009. www.theannals.com, DOI 10.1345/aph.1L690