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The present randomized controlled study aimed to investigate the in vivo distribution of constituents or metabolites of the standardized maritime pine bark extract Pycnogenol\(^{®}\). Thirty-three patients with severe osteoarthritis scheduled for a knee arthroplasty were randomized to receive either 200 mg per day Pycnogenol\(^{®}\) (P+) or no treatment (Co) over three weeks before surgery. Serum, blood cells, and synovial fluid samples were analyzed using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization (LC-ESI/MS/MS). Considerable interindividual differences were observed indicating pronounced variability of the polyphenol pharmacokinetics. Notably, the highest polyphenol concentrations were not detected in serum. Catechin and taxifolin primarily resided within the blood cells while the microbial catechin metabolite δ-(3,4-dihydroxy-phenyl)-γ-valerolactone, ferulic, and caffeic acid were mainly present in synovial fluid samples. Taxifolin was detected in serum and synovial fluid exclusively in the P+ group. Likewise, no ferulic acid was found in serum samples of the Co group. Calculating ratios of analyte distribution in individual patients revealed a simultaneous presence of some polyphenols in serum, blood cells, and/or synovial fluid only in the P+ group. This is the first evidence that polyphenols distribute into the synovial fluid of patients with osteoarthritis which supports rationalizing the results of clinical efficacy studies.
Urinary, Circulating, and Tissue Biomonitoring Studies Indicate Widespread Exposure to Bisphenol A
(2012)
Bisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to which humans are exposed may cause adverse health effects. We examined many possibilities for why biomonitoring and toxicokinetic studies could come to seemingly conflicting conclusions. More than 80 published human biomonitoring studies that measured BPA concentrations in human tissues, urine, blood, and other fluids, along with two toxicokinetic studies of human BPA metabolism were examined. Unconjugated BPA was routinely detected in blood (in the nanograms per milliliter range), and conjugated BPA was routinely detected in the vast majority of urine samples (also in the nanograms per milliliter range). In stark contrast, toxicokinetic studies proposed that humans are not internally exposed to BPA. Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA. The two toxicokinetic studies that suggested human BPA exposure is negligible have significant deficiencies, are directly contradicted by hypothesis-driven studies, and are therefore not reliable for risk assessment purposes.
Aims: The aim of the current study was to establish a simple and yet as much as possible physiologic approach for a simulation of the pulmonary absorption process to compare different inhaled drugs or drug formulations.
Methodology: We designed a dialysis setting that allowed monitoring the drug release from human lung tissue into a continuous-flow plasma compartment. For proof-of-concept experiments we chose the glucocorticoid fluticasone propionate (FP) as model compound. For subsequent experiments we selected a commercially available metered dose inhaler delivering a fixed combination of the short-acting ß2-agonist fenoterol and the muscarinic antagonist ipratropium bromide.
Results: With the novel dynamic dialysis model we observed high drug transport rates from the lung tissue into plasma including an elimination phase. The concentration profile in the plasma compartment of our model system was similar to the plasma concentration courses after inhalation of FP. Compared to FP significantly higher drug fractions of fenoterol and ipratropium bromide were released into plasma and the transfer of ipratropium was more pronounced compared to fenoterol. Again, concentration profiles in plasma were alike to those described in clinical studies.
Conclusion: We suggest that this model is appropriate for rapid assessment of comparative diffusion behaviour of drugs or drug formulations from lung tissue into plasma.