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.

Application of Cornelian Cherry Iridoid-Polyphenolic Fraction and Loganic Acid to Reduce Intraocular Pressure.

One of the most common diseases of old age in modern societies is glaucoma. It is strongly connected with increased intraocular pressure (IOP) and could permanently damage vision in the affected eye. As there are only a limited number of chemical compounds that can decrease IOP as well as blood flow in eye vessels, the up-to-date investigation of new molecules is important. The chemical composition of the dried Cornelian cherry (Cornus mas L.) polar, iridoid-polyphenol-rich fraction was investigated. Loganic acid (50%) and pelargonidin-3-galactoside (7%) were found as the main components. Among the other constituents, iridoid compound cornuside and the anthocyans cyanidin 3-O-galactoside, cyanidin 3-O-robinobioside, and pelargonidin 3-O-robinobioside were quantified in the fraction. In an animal model (New Zealand rabbits), the influence of loganic acid and the polyphenolic fraction isolated from Cornelian cherry fruit was investigated. We found a strong IOP-hypotensive effect for a 0.7% solution of loganic acid, which could be compared with the widely ophthalmologically used timolol. About a 25% decrease in IOP was observed within the first 3 hours of use.

[Cefprozil in the treatment of chronic maxillary sinusitis. Clinical and microbiological effectiveness and penetration into sinuses examination]. / Cefprozil w leczeniu przewleklego zapalenia zatok szczekowych. Ocena kliniczna, mikrobiologiczna oraz skutecznosci przenikania leku do zatok.

UNLABELLED: 40 patients with exacerbation of a chronic maxillary sinusitis were examined. Sinus puncture was performed (sinoject) in all of the patients. Before the treatment (500 mg cefprozil orally twice a day, the recommended duration of therapy was ten days) and on the fifth day, the microorganisms from sinus were isolated (the bacteriological culture, antibiogram and MIC were determined). On the second and the fifth day, blood cefprozil level and the presence of cefprozil in the washings from maxillary sinuses were investigated. RESULTS: 17 pathogens were isolated from maxillary sinuses, only two of them were anaerobic. The bacterial strains: Staphylococcus (55%), E.coli (15%), Klebsiella (10%) and 20% of others, were found. Four of them (23.5%) were resistant to cefprozil. In all patients cefprozil was identified in maxillary sinuses (0.87-2.52 ug/ml). The value of MIC were from 0.094 to 2.0 ug/ml. A satisfactory clinical response was observed in 92.5% persons but the eradication of pathogens was obtained in 70%. The adverse clinical events (diarrhea) were observed only in one patient (2.5%). CONCLUSIONS: cefprozil well penetrates into inflammable mucous membrane of maxillary sinuses. Cefprozil obtains efficient bactericidal concentration in relation to sensitive bacteria on the fifth day of therapy. It is also well tolerated by the patients.

Influence of nifedipine, nitrendipine and verapamil at low concentration on antipyrine metabolism examined by extracorporeal rat liver perfusion.

An increase in calcium ion concentration in the cytoplasm due to the influence of various toxic agents causes disturbances in the structure and function of hepatocytes, leading to their damage and even death. Calcium ions enter the cell mostly through calcium channels, therefore, it has been suggested that calcium channel inhibitors (CCI) could protect hepatocytes from the action of toxic substances. The present study investigated the effect of the selected CCI (nifedipine, nitrendipine and verapamil) on liver function, measured by the efficiency of oxidation reaction, in this case by determination of the rate of antipyrine metabolism. The experiment was carried out using the method of extracorporeal liver perfusion (ELP). None of the studied CCI applied at a concentration of 50 micromol/l increased the rate of antipyrine metabolism over the whole period of ELP. However, supplementation of perfusion fluid with nifedipine, nitrendipine or verapamil at a concentration of 20 micromol/l considerably improved metabolic liver efficiency during the second hour of perfusion, i.e. at the time, when large number of hepatocytes started to perish, which could indicate protective action of the tested CCI. However, the CCI-induced acceleration of antipyrine metabolism was not a result of their influence on calcium channels, since these drugs block calcium channels, when given at the concentrations as high as 100-400 micromol/l. Moreover, it seems that facilitation of antipyrine metabolism during ELP was not due to their action on microsomal enzymes because CCI were administered at very low concentrations, besides, they are metabolic inhibitors, and not inducers. The present experiment suggests that low concentrations of CCI can exert hepatoprotective effect. However, confirmation of this conclusion requires further studies using other experimental methods.