Scope Xanthohumol (XN) is a bioactive prenylflavonoid from hops. A single-dose pharmacokinetic (PK) study was conducted in men (n=24) and women (n=24) to determine dose-concentration relationships. Methods and results Subjects received a single oral dose of 20, 60, or 180 mg XN. Blood was collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, and 120 h. Plasma levels of XN and its metabolites, isoxanthohumol (IX), 8-prenylnaringenin (8PN) and 6-prenylnaringenin (6PN) were measured by LC-MS/MS. Xanthohumol and IX conjugates were dominant circulating flavonoids among all subjects. Levels of 8PN and 6PN were undetectable in most subjects. The XN PK profile showed peak concentrations around 1h and between 4-5h after ingestion. The maximum XN concentrations (Cmax) were 45±7 μg/L, 67±11 μg/L, and 133±23 μg/L for the 20, 60, and180 mg dose, respectively. Using non-compartmental modeling, the area under the curves (AUC0→∞) for XN were 92±68 h×μg/L, 323±160 h×μg/L, and 863±388 h×μg/L for the 20, 60, and 180 mg dose, respectively. The mean half-life of XN was 20 h for the 60 and 18 h for the 180 mg dose. Conclusion Xanthohumol has a distinct biphasic absorption pattern with XN and IX conjugates being the major circulating metabolites.

IntroductionWe have previously reported results of precipitation studies for neonatal parenteral nutrition solutions containing calcium chloride and sodium phosphate using visual methods to determine compatibility. The purpose of this study was to do further testing of compatibility for solutions containing calcium chloride using more sensitive methods.MethodsSolutions of Trophamine (Braun Medical Inc, Irvine, CA) and Premasol (Baxter Pharmaceuticals, Deerfield, IL) were compounded with calcium chloride and potassium phosphate. Controls contained no calcium or phosphate. After incubation at 37° for 24 hours solutions without visual precipitation were analyzed to determine mean particle size using dynamic light scattering from a laser light source.ResultsParticle sizes were similar for control solutions and those without visual precipitation and a mean particle size <1000 nm. Compatible solutions were defined as those with added calcium and phosphate with no visual evidence of precipitation and mean particle size <1000 nm. In solutions containing 2.5–3% amino acids and 10 mmol/L of calcium chloride the maximum amount of potassium phosphate that was compatible was 7.5 mmol/L.ConclusionMaximum amounts of phosphate that could be added to parenteral nutrition solutions containing Trophamine and calcium chloride were about 7.5–10 mmol/L less for a given concentration of calcium based upon laser methodology compared to visual techniques to determine compatibility. There were minor differences in compatibility when adding calcium chloride and potassium phosphate to Premasol versus Trophamine.

Current findings suggest flavonoids might aid in prevention and/or mitigation of cardiovascular disease and type II diabetes. Specifically, xanthohumol (XN), a prenylflavonoid from hops, has recently been shown to improve glucose and lipid homeostasis in obese rodents. However, there is limited data on XN metabolism in humans. A study was conducted in healthy men (n=24) and women (n=24) to determine basic aspects of XN pharmacokinetics (PK). Subjects were randomized on age and gender and given one of the following oral doses: 20, 60, or 180 mg XN. Blood was collected at 0, 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, 96, and 120 h. Plasma samples were analyzed for XN and its metabolites: isoxanthohumol (IX), 8‐prenylnaringenin (8PN) and 6‐prenylnaringenin (6PN) using LC‐MS/MS. PK parameters were estimated by fitting a non‐compartmental model to the experimental results. XN and IX were the dominant circulating metabolites among all subjects. Levels of 8PN were very low in some subjects (n=5) and not detectable in others. Levels of 6PN were not detectable in all subjects. The Cmax was 41±30 μg/L for the 20 mg dose, 67±40 μg/L for the 60 mg dose, and 133±97μg/L for the 180 mg dose. The AUC0→∞was 84±68 h*μg/L, 286±155 h*μg/L, and 809±384 h*μg/L for the 20, 60, and 180 mg dose, respectively. This work was supported by National Institutes of Health (R21AT005294).