Silke C. Mueller

Pharmacokinetics and bioavailability of quercetin glycosides in humans

Due to its potentially beneficial impact on human health, the polyphenol quercetin has come into the focus of medicinal interest. However, data on the bioavailability of quercetin after oral intake are scarce and contradictory. Previous investigations indicate that the disposition of quercetin may depend on the sugar moiety of the glycoside or the plant matrix. To determine the influence of the sugar moiety or matrix on the absorption of quercetin, two isolated quercetin glycosides and two plant extracts were administered to 12 healthy volunteers in a four‐way crossover study. Each subject received an onion supplement or quercetin‐4′‐O‐glucoside (both equivalent to 100 mg quercetin), as well as quercetin‐3‐O‐rutinoside and buckwheat tea (both equivalent to 200 mg quercetin). Samples were analyzed by HPLC with a 12‐channel coulometric array detector. In human plasma, only quercetin glucuronides, but no free quercetin, could be detected. There was no significant difference in the bioavailabilityand pharmacokinetic parameters between the onion supplement and quercetin‐4′‐O‐glucoside. Peak plasma concentrations were 2.3 ± 1.5 μg•mL−1 and 2.1 ± 1.6 μg•mL−1 (mean ± SDJ and were reached after 0.7 ± 0.2 hours and 0.7 ± 0.3 hours, respectively. After administration of buckwheat tea and rutin, however, peak plasma levels were—despite the higher dose—only 0.6 ± 0.7 μg•mL−1 and 0.3 ± 0.3 μg•mL−1, respectively. Peak concentrations were reached 4.3 ± 1.8 hours after administration of buckwheat tea and 7.0 ± 2.9 hours after ingestion of rutin. The terminal elimination half‐life was about 11 hours for all treatments. Thus, the disposition of quercetin in humans primarily depends on the sugar moiety. To a minor extent, the plant matrix influences both the rate and extent of absorption in the case of buckwheat tea administration compared with the isolated compound. The site of absorption seems to be different for quercetin‐4′‐O‐glucoside and quercetin‐3‐O‐rutinoside. The significance of specific carriers on the absorption of quercetin glycosides, as well as specific intestinal b‐glucosidases, needs to be further evaluated.

Effect of St John's Wort Dose and Preparations on the Pharmacokinetics of Digoxin

St Johns wort preparations vary in composition, main constituents, formulation, and daily dose administered. The aim of the study was to evaluate the possible pharmacokinetic interaction of marketed St Johns wort formulations and doses with digoxin.

Adverse drug reactions in Germany: direct costs of internal medicine hospitalizations

German hospital reimbursement modalities changed as a result of the introduction of Diagnosis Related Groups (DRG) in 2004. Therefore, no data on the direct costs of adverse drug reactions (ADRs) resulting in admissions to departments of internal medicine are available. The objective was to quantify the ADR‐related economic burden (direct costs) of hospitalizations in internal medicine wards in Germany.

Pharmacokinetics of Piperacillin-Tazobactam in Anuric Intensive Care Patients during Continuous Venovenous Hemodialysis

ABSTRACT The pharmacokinetics of piperacillin-tazobactam were investigated in eight anuric intensive care patients treated by continuous venovenous hemodialysis (CVVHD). The elimination half-life of piperacillin was 4.3 ± 1.2 h, and that of tazobactam was 5.6 ± 1.3 h. The contribution of CVVHD to the overall elimination was relevant (>25%) for both drugs.

Perioperative antibiotic prophylaxis in maxillofacial surgery: penetration of clindamycin into various tissues.

Although clindamycin is recommended for prophylactic use in oral and maxillofacial surgery, there is little data available regarding its ability to provide sufficient tissue concentrations at the operative site. We investigated tissue samples from 31 patients, who had to undergo oral and maxillofacial surgery and who received at least one dose of 600 mg clindamycin i.v. preoperatively, to determine clindamycin tissue concentrations in muscle, oral mucosa, fatty tissue, skin and bone between 15 min and 8 h after administration. After homogenization, clindamycin concentration was determined by bioassay. It was demonstrated that clindamycin concentrations above the MIC90 of those pathogens most likely to cause contamination were reached in all kinds of tissues investigated. Already 15 min after administration, tissue concentrations above the MIC90 were reached and were still detectable in the last samples taken between 4 and 8 h after the last clindamycin administration. From the pharmacokinetic point of view, clindamycin is suitable for perioperative prophylaxis during oral and maxillofacial surgery providing sufficient tissue concentrations with no intraoperative additional dosage necessary unless procedures exceed 4 h duration.

Intraindividual long term stability and response corridors of cytokines in healthy volunteers detected by a standardized whole-blood culture system for bed-side application

BackgroundThe variation of immune cell activities over time is an immanent property of the human immune system, as can be measured by the stimulated secretion of cytokines in cell cultures. However, inter-individual variability is considerably higher. Especially the latter is the major reason why it has not been possible to establish international standard values for cytokines as was possible for other parameters, such as leukocyte sub-population numbers. In this trial, a highly standardized whole-blood culture model (TrueCulture®), developed to characterise drug effects on cells of the human immune system in clinical trials, was used to analyse cytokine patterns in the blood samples of 12 healthy subjects over a period of one month.MethodsAfter an overnight fast, 12 healthy subjects donated blood three times a week on three consecutive days over a period of 4 weeks. TruCulture® blood collection and whole-blood culture systems were used to measure whole-blood leukocyte stimulation. The levels of IL-2, IL-5, IL-13, IL-6, IL-8, IL-10, IFNγ, and MCP-1 in the culture supernatants were quantified by sandwich ELISA.ResultsThe pattern of cytokine concentrations in the supernatants of the stimulated whole-blood cultures was highly individual, but considerably stable over the whole observation period of 4 weeks.ConclusionsBy using TruCulture® it seems feasible to determine subject-specific cytokine reference patterns, for example under healthy conditions, or before starting an experimental treatment, e.g. during a clinical trial, against which changes in the behaviour of the immune system can be detected more accurately in future.

Induction of CYP3A by St. Johns Wort (SJW) depends on hyperforin (HYF) dose

Induction of CYP3A by SJW with high HYF content is known. SJW products vary in the amount of main constituents. The aim of the study was to evaluate the influence of SJW preparations with low and high HYF content on CYP3A function.