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

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. CONCLUSIONS: The same doses of XN may be administered to male and female subjects, as its pharmacokinetics is not affected by sex.

Effect of long-term administration of ranitidine, a histamine H2 receptor antagonist, on bone metabolism in young growing rats.

BACKGROUND: Histamine regulates function of osteoclasts and osteoblasts, however data regarding the influence of histamine H2 receptors antagonists on bone tissue are ambiguous. Factors that influence growing skeleton may have an important impact on the peak bone mass and future risk of fractures. The aim of our study was the assessment of influence of ranitidine, on growing bones. METHODS: The experiment was carried out on young male Wistar rats divided into two groups receiving either ranitidine (10mg/kg ip) or vehicle. RESULTS: A significant decrease in femoral BMD in ranitidine-treated rats (R) compared to vehicle-treated ones (C) was detected (0.262±0.009g/cm2vs. 0.271 ±0.007g/cm2, p<0.05). In group R we observed elevated serum C-terminated telopeptide of type I collagen (CTX) level with concomitantly lowered serum osteocalcin (OC) concentration comparing to control group (151.2±27.2pg/ml vs. 101.5±55.6, p<0.05 and 229.1±50.0pg/ml vs. 292.0±52.9, p<0.05, respectively). Serum concentration of inorganic phosphorus was lower in group R than in group C (134±13mmol/L vs. 157±28mmol/L, p<0.05). CONCLUSIONS: Long-term administration of ranitidine increases bone resorption and decreases bone formation in growing rats leading to decrease in BMD.