Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 9, September, p. 1101–1109

doi: 10.17219/acem/126293

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Pharmacokinetics of xanthohumol in rats of both sexes after oral and intravenous administration of pure xanthohumol and prenylflavonoid extract

Beata Nowak1,A,B,C,D,F, Błażej Poźniak2,C,D,E,F, Jarosław Popłoński3,A,C,D,E,F, Łukasz Bobak3,C,E,F, Agnieszka Matuszewska1,B,E,F, Joanna Kwiatkowska1,B,F, Wojciech Dziewiszek1,B,E,F, Ewa Huszcza3,A,C,E,F, Adam Szeląg1,A,E,F

1 Department of Pharmacology, Faculty of Medicine, Wroclaw Medical University, Poland

2 Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, Poland

3 Department of Chemistry, Faculty of Biotechnology and Food Science, Wroclaw University of Environmental and Life Sciences, Poland

Abstract

Background. Female inflorescences of hops (Humulus lupulus L.) are wildly used in the brewing industry. Hops have been also used for ages in folk medicine. Xanthohumol (XN) is a most abundant prenylated flavonoid present in hops.
Objectives. To determine pharmacokinetic parameters and bioavailability of pure XN and XN given in prenylflavonoid extract obtained from spent hops (HOP).
Material and Methods. Fifty-six Wistar rats (28 females and 28 males) were administered with XN or HOP. Xanthohumol was administered either intravenously (iv.) (10 mg/kg) or orally (per os (p.o.)) (40, 100 and 200 mg/kg). Extract obtained from spent hops was administered p.o. and its doses were based on XN content (doses were equivalent to XN dose of 40, 100 and 200 mg/kg, respectively). After administration of XN or HOP serum, XN concentration was measured at different time points (0, 0.25, 0.5, 1, 2, 4, 6, 12, 24, 48, 72, and 96 h). Non-compartmental analysis was used to assess the pharmacokinetics (PK) of XN in rats.
Results. The XN PK in rats after intravenous administration is characterized by extensive distribution followed by delayed elimination from the body. Enterohepatic recirculation is likely to play a role in XN PK. Some fraction of the orally administered XN reaches central compartment rapidly; however, the overall absorption is very limited and probably saturable. The formulation-dependent factors also play an important role in the bioavailability of the drug. Although the CMAX concentration was higher in female rats receiving XN orally comparing to males, the other pharmacokinetic parameters were unaffected by the rats’ sex.
Conclusion. The same doses of XN may be administered to male and female subjects, as its pharmacokinetics is not affected by sex.

Key words

bioavailability, pharmacokinetics, prenylflavonoid, rat, xanthohumol

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