Pharmacokinetics and systemic endocrine effects of the phyto-oestrogen 8-prenylnaringenin after single oral doses to postmenopausal women

British Journal of Clinical Pharmacology

Volumn 62, Issue 3, 2006, Pages 288-296

  Rad, M ^a   Humpel M ^b   Schaefer, O ^b   Schoemaker, R C ^a   Schleuning, W D ^c   Cohen, A F ^a   Burggraaf, J ^a  

^a CENTRE FOR HUMAN DRUG RESEARCH   (Netherlands)

^b BAYER PHARMA AG   (Germany)

^c NOXXON PHARMA AG   (Germany)

Author keywords

8 PN; Enterohepatic recirculation; HRT; LH; Phyto oestrogen

Indexed keywords

8 PRENYLNARINGENIN; FLAVONE DERIVATIVE; FOLLITROPIN; LUTEINIZING HORMONE; PHYTOESTROGEN; PLACEBO; UNCLASSIFIED DRUG;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; CONJUGATE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG FECES LEVEL; DRUG METABOLISM; DRUG TOLERABILITY; DRUG URINE LEVEL; ENTEROHEPATIC CIRCULATION; EPISTAXIS; ERYTHEMA; FEMALE; FOLLITROPIN BLOOD LEVEL; GASTROINTESTINAL SYMPTOM; HEADACHE; HEMATOMA; HORMONE SUBSTITUTION; HUMAN; HUMAN EXPERIMENT; INCIDENCE; LUTEINIZING HORMONE BLOOD LEVEL; NORMAL HUMAN; POSTMENOPAUSE; PRIORITY JOURNAL; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RESTLESSNESS; SINGLE DRUG DOSE; TREATMENT OUTCOME; UPPER RESPIRATORY TRACT INFECTION;

ADMINISTRATION, ORAL; AGED; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; FLAVANONES; FOLLICLE STIMULATING HORMONE; HUMANS; LUTEINIZING HORMONE; MIDDLE AGED; PHYTOESTROGENS; POSTMENOPAUSE; RECEPTORS, ESTROGEN;

EID: 33747067740     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2006.02656.x     Document Type: Article

References (27)

1. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-33.
2. Lemay A. The relevance of the Women's Health Initiative results on combined hormone replacement therapy in clinical practice. J Obstet Gynaecol Can 2002; 24: 711-5.
3. Nelson HD, Humphrey LL, Nygren P, Teutsch SM, Allan JD. Postmenopausal hormone replacement therapy: scientific review. JAMA 2002; 288: 872-81.
4. Barrett-Connor E, Stuenkel CA. Hormone replacement therapy (HRT)-risks and benefits. Int J Epidemiol 2001; 30: 423-6.
5. Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003; 362: 419-27.
6. Krebs EE, Ensrud KE, MacDonald R, Wilt TJ. Phytoestrogens for treatment of menopausal symptoms: a systematic review. Obstet Gynecol 2004; 104: 824-36.
7. Nagata C, Takatsuka N, Kawakami N, Shimizu H. Soy product intake and hot flashes in Japanese women: results from a community-based prospective study. Am J Epidemiol 2001; 153: 790-3.
8. Milligan SR, Kalita JC, Van Pocock VDKV, Stevens JF, Deinzer ML, Rong H, De Keukeleire D. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab 2000; 85: 4912-5.
9. Gester S, Metz P, Zierau O, Vollmer G. An efficient synthesis of the potent phytoestrogens 8-prenylnaringenin and 6-(1,1-dimethylallyl) naringenin by europium (III)-catalyzed Claisen rearrangement. Tetrahedron 2001; 57: 1015-8.
10. Schaefer O, Hümpel M, Fritzemeier KH, Bohlmann R, Schleuning WD. 8-Prenyl naringenin is a potent ERalpha selective phytoestrogen present in hops and beer. J Steroid Biochem Mol Biol 2003; 84: 359-60.
11. Hümpel M, Isaksson P, Schaefer O, Kaufmann U, Ciana P, Maggi A, Schleuning WD. Tissue specificity of 8-prenylnaringenin: protection from ovariectomy induced bone loss with minimal trophic effects on the uterus. J Steroid Biochem Mol Biol 2005; 97: 299-305.
12. O'Connell MB. Pharmacokinetic and pharmacologic variation between different estrogen products. J Clin Pharmacol 1995; 35: 18S-24S.
13. Morgan JB. Use of non-absorbable markers in studies of human nutrient absorption. Hum Nutr Appl Nutr 1986; 40: 399-411.
14. Schaefer O, Bohlmann R, Schleuning WD, Schulze-Forster K, Hümpel M. Development of a radioimmunoassay for the quantitative determination of 8-prenylnaringenin in biological matrices. J Agric Food Chem 2005; 53: 2881-9.
15. Hümpel M, Illi V, Milius W, Wendt H, Kurowski M. The pharmacokinetics and biotransformation of the new benzodiazepine lormetazepam in humans. I. Absorption, distribution, elimination and metabolism of lormetazepam-5-14C. Eur J Drug Metab Pharmacokinet 1979; 4: 237-43.
16. Louton T, Kuhnz W, Dibbelt L, Knuppen R. Weighted serum pools in comparison to the trapezoidal rule for estimating AUCs for ethinyl estradiol. The relationship of the variance of the determination to the interindividual variance. Eur J Clin Pharmacol 1994; 46: 77-81.
17. Russell L, Hicks GS, Low AK, Shepherd JM, Brown CA. Phytoestrogens: a viable option? Am J Med Sci 2002; 324: 185-8.
18. Kitaoka M, Kadokawa H, Sugano M, Ichikawa K, Taki M, Takaishi S, Iijima Y, Tsutsumi S, Boriboon M, Akiyama T. Prenylflavonoids: a new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure-activity relationship. Planta Med 1998; 64: 511-5.
19. Milligan S, Kalita J, Pocock V, Heyerick A, De Cooman L, Rong H, De Keukeleire D. Oestrogenic activity of the hop phyto-oestrogen, 8-prenylnaringenin. Reproduction 2002; 123: 235-42.
20. Milligan SR, Kalita JC, Heyerick A, Rong H, De Cooman L, De Keukeleire D. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab 1999; 84: 2249-52.
21. Stevens JF, Page JE. Xanthohumol and related prenylflavonoids from hops and beer: to your good health! Phytochemistry 2004; 65: 1317-30.
22. Rong H, Boterberg T, Maubach J, Stove C, Depypere H, Van Slambrouck S, Serreyn R, De Keukeleire D, Mareel M, Bracke M. 8-Prenylnaringenin, the phytoestrogen in hops and beer, upregulates the function of the E-cadherin/catenin complex in human mammary carcinoma cells. Eur J Cell Biol 2001; 80: 580-5.
23. Shirataki Y, Motohashi N, Tani S, Sakagami H, Satoh K, Nakashima H, Mahapatra SK, Ganguly K, Dastidar SG, Chakrabarty AN. In vitro biological activity of prenylflavanones. Anticancer Res 2001; 21: 275-80.
24. Pepper MS, Hazel SJ, Hümpel M, Schleuning WD. 8-prenylnaringenin, a novel phytoestrogen, inhibits angiogenesis in vitro and in vivo. J Cell Physiol 2004; 199: 98-107.
25. Yen SS, Martin PL, Burnier AM, Czekala NM, Greaney MO Jr, Callantine MR. Circulating estradiol, estrone and gonadotropin levels following the administration of orally active 17beta-estradiol in postmenopausal women. J Clin Endocrinol Metab 1975; 40: 518-21.
26. Englund DE, Johansson ED. Plasma levels of oestrone, oestradiol and gonadotrophins in postmenopausal women after oral and vaginal administration of conjugated equine oestrogens (Premarin). Br J Obstet Gynaecol 1978; 85: 957-64.
27. Nikolic D, Li Y, Chadwick LR, Grubjesic S, Schwab P, Metz P, van Breemen RB. Metabolism of 8-prenylnaringenin, a potent phytoestrogen from hops (Humulus lupulus), by human liver microsomes. Drug Metab Dispos 2004; 32: 272-9.