Calystegines are Potential Urine Biomarkers for Dietary Exposure to Potato Products.

SCOPE: Metabolites derived from specific foods present in urine samples can provide objective biomarkers of food intake (BFIs). This study investigated the possibility that calystegines (a class of iminosugars) may provide BIFs for potato (Solanum tuberosum L.) product exposure. METHODS AND RESULTS: Calystegine content is examined in published data covering a wide range of potato cultivars. Rapid methods are developed for the quantification of calystegines in cooked potato products and human urine using triple quadrupole mass spectrometry. The potential of calystegines as BFIs for potato consumption is assessed in a controlled food intervention study in the United Kingdom and validated in an epidemiological study in Portugal. Calystegine concentrations are reproducibly above the quantification limit in first morning void urines the day after potato consumption, showing a good dose-response relationship, particularly for calystegine A3 . The design of the controlled intervention mimicks exposure to a typical UK diet and showed that neither differences in preparation/cooking method or influence of other foods in the diet has significant impact on biomarker performance. Calystegine biomarkers also perform well in the independent validation study. CONCLUSION: It is concluded that calystegines have many of the characteristics needed to be considered as specific BFIs for potato product intake.

The role of p-glycoprotein in limiting brain penetration of the peripherally acting anticholinergic overactive bladder drug trospium chloride.

The aim of the present study was to characterize the role of the drug-efflux transporter P-glycoprotein (P-gp) for the disposition of trospium chloride, a widely used anticholinergic drug for the treatment of overactive bladder. P-gp-deficient mdr1a,b(-/-) knockout mice were given either 1 mg/kg trospium chloride orally or 1 mg/kg intravenously to analyze brain penetration, intestinal secretion, and hepatobiliary excretion of the drug. The concentrations of trospium chloride in the brain were up to 7 times higher in the mdr1a,b(-/-) knockout mice compared with wild-type mice (p < 0.05), making P-gp a limiting factor for the blood-brain barrier penetration of this drug. Moreover, the residence time of the drug in the central nervous system was significantly prolonged in mdr1a,b(-/-) knockout mice. Apart from the blood-brain barrier, P-gp also had significant effects on the overall pharmacokinetics of trospium chloride. In the mdr1a,b(-/-) knockout mice, hepatobiliary excretion and intestinal secretion were significantly reduced compared with the wild-type mice. Our study indicates that the multidrug resistance transporter P-gp is a major determinant for the distribution of trospium chloride in the body and highly restricts its entry into the brain.

Dosimetry of the dopamine transporter radioligand 18F-FPCIT in human subjects.

UNLABELLED: This study was designed to evaluate the radiation dosimetry in human subjects for a new radiopharmaceutical, N-(3-(18)F-fluoropropyl)-2beta-carbomethoxy-3beta-(4-iodophenyl)nortropane ((18)F-FPCIT). The goal was to determine a limiting dose consistent with accepted guidelines for use in clinical studies and to compare the radiation burden with other agents such as (123)I-FPCIT, (18)F-fluorodopa, and (18)F-FDG. METHODS: Dynamic PET scans of the urinary bladder were obtained in 6 subjects; 2 subjects had brain scans and 5 subjects had scans of the thorax or abdomen. Regions of interest were placed over composite images of each organ for which activity was visualized to generate time-activity curves. Doses were calculated from residence times using the MIRDOSE3 program. RESULTS: The critical organ for dosimetry is the urinary bladder wall with a dose of 0.0586 +/- 0.0164 mGy/MBq. The dose comes primarily (97.2%) from activity in the urinary bladder contents. The dose is lower than any of the other agents used commonly in PET to assess dopaminergic function. The effective dose equivalent (0.0120 mGy/MBq) is also lower than comparable compounds. CONCLUSION: (18)F-FPCIT has favorable dosimetry when compared with other agents used to study dopaminergic function. Doses as high as 853 MBq (23 mCi) may be given to adult patients and remain within accepted guidelines.

Determination of the bioavailability of the quaternary compound trospium chloride in man from urinary excretion data.

For the quaternary compound trospium chloride (Spasmex) which is used as an anticholinergic agent a new sensitive assay method has been developed that allows the quantitative determination of the drug in human urine and plasma. Using this method it was possible to obtain pharmacokinetic data from plasma levels and urinary excretion, and to determine the bioavailability in man. Quantitative determination is performed by alkaline hydrolysis to the corresponding spiroalcohol, ion-pair extraction with dipicrylamine, subsequent derivatization with the fluorophor benoxaprofen chloride, and ion-pair chromatographic separation on a reversed-phase column with chloride as the counter-ion using a mixture of acetonitrile and water. In healthy volunteers (n = 6) the plasma concentration time curve after intravenous administration of 0.5 mg trospium chloride could be described by an open two-compartment model. The mean half-lives were 2.7 and 97 min, respectively. After oral administration of 10 mg the highest concentration found in plasma was 1.4 ng trospium chloride/ml. 55% of the given dose were excreted unchanged into urine within 48 h after i.v. administration, the corresponding value after oral administration was 1.6%. If no hydrolysis is carried out in urine samples the spiroalcohol can be detected as metabolite of trospium. Within 48 h after i.v. administration 4% and after oral administration 0.3% of the given dose are excreted into urine as spiroalcohol. From the cumulative excretion of trospium into urine within 48 h a mean bioavailability of 2.9% was calculated.

Radioimmunoassay of trospiumchloride, a quaternary tropane derivative.

A specific radioimmunoassay (RIA) has been developed for the determination of picogram amounts of trospiumchloride, an anticholinergic agent, from unpurified serum and urine samples. Practically no interference was observed for various potential crossreacting compounds tested. The method is sensitive and excellent values for accuracy, precision and correlation were obtained.

Fluorimetric determination of the quaternary compound trospium and its metabolite in biological material after derivatization with benoxaprofen chloride.

The quantitative determination of the quaternary compound trospium and the corresponding spiroalcohol is described for human biological material. Analysis is performed by alkaline hydrolysis, ion-pair extraction into chloroform, subsequent derivatization with the flurophor benoxaprofen chloride and high-performance liquid chromatographic separation on a reversed-phase column. The limit of quantitation is ca. 1 pmol (1.03 pmol=lng of trospium chloride) per millilitre of plasma.