0000000000206621
AUTHOR
Hildegard Spahn-langguth
showing 9 related works from this author
Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats.
2001
The expression of P-glycoprotein is induced in cell cultures upon exposure to various inducers. Therefore, the aim of the present study was to evaluate the in-vivo relevance of this observation, i.e. the influence of chronic pretreatments with selected drugs -- all of which are ligands to P-glycoprotein (P-gp) as demonstrated in radioligand binding studies and all of which have some or a considerable effect on P-gp expression in Caco-2 cells -- on the effective intestinal permeabilities of the model compound talinolol in rats employing in-situ single-pass intestinal perfusion of three different gut segments. Talinolol was selected, because it shows high selectivity for one of the exsorptive…
Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates.
2004
Abstract The pharmacokinetics of antipsychotic drugs has become an integral part in understanding their pharmacodynamic activity and clinical effects. In addition to metabolism aspects, carrier-mediated transport, particularly secretion by ABC transporters, has been discussed as potentially relevant for this group of therapeutics. In this study, the psychoactive compounds perphenazine, flupentixol, domperidone, desmethyl clozapine, haloperidol, fluphenazine, fluvoxamine, olanzapine, levome-promazine, perazine, desmethyl perazine, clozapine, quetiapine and amisulpride were characterized in terms of P-glycoprotein (P-gp) affinity and transport. Experimental methods involved a radioligand disp…
Determination of triamterene and its main metabolite hydroxytriamterene sulfate in human urine by capillary electrophoresis using ultraviolet absorba…
2002
Abstract Two capillary electrophoresis methods have been developed for the direct determination of triamterene and its main metabolite hydroxytriamterene sulfate in human urine. Analytes were detected using conventional UV detection as well as laser-induced fluorescence (LIF) detection with an HeCd-laser operating at a wavelength of 325 nm. The results of both detection techniques were compared. Indeed, the limit of quantification was eightfold lower using LIF detection (50 ng/ml) in comparison to UV detection (400 ng/ml). As no interference due to endogenous urine compounds was observed, direct urine analysis was feasible. Analysis was very simple and fast—one run could be performed within…
Inhibition of Folic Acid Uptake by Catechins and Tea Extracts in Caco-2 Cells
2006
In this present study it was aimed to determine whether the catechins contained in green tea and the whole extracts of Camellia sinensis (Theaceae) inhibit the uptake of folic acid by Caco-2 cell monolayers. Our results indicate that (-)-epigallocatechin 3-gallate (EGCG) and (-)-epicatechin 3-gallate (ECG) inhibit cellular folic acid uptake with IC50 values of 34.8 micromol/L and 30.8 micromol/L, respectively. Furthermore, green and black tea extracts were also found to inhibit folic acid uptake with IC50 values of approximately 7.5 and 3.6 mg/mL, respectively. According to these results, simultaneous intake of tea and folic acid may inhibit intestinal folic acid absorption. The consequence…
Influence of green and black tea on folic acid pharmacokinetics in healthy volunteers: potential risk of diminished folic acid bioavailability
2008
Previous in vitro studies using Caco-2 cell monolayers suggested a possible interaction between green and black tea and folic acid at the level of intestinal absorption. The main purpose of the present study was to investigate a possible pharmacokinetic interaction between tea and folic acid in healthy volunteers. In an open-labeled randomized cross-over study, the pharmacokinetic interaction between tea and folic acid (0.4 mg and 5 mg) was investigated in healthy volunteers. Water was used as the reference drink. Subjects ingested 0.4 mg folic acid tablets with water, green or black tea (0.3 g extract/250 ml) or 5 mg folic acid tablets with water or green tea (0.3 g extract/250 ml). Blood …
Role of P‐glycoprotein‐mediated secretion in absorptive drug permeabiity: An approach using passive membrane permeability and affinity to P‐glycoprot…
1999
Abstract It has been shown in vivo and in vitro that P‐glycoprotein (P‐gp) may be able to influence the permeability of its substrates across biological membranes. However, the quantitative contribution of the secretion process mediated by P‐gp on the overall permeability of membranes has not been determined yet. In particular, observations need to be clarified in which substrates showing high affinity to P‐glycoprotein, e.g., verapamil, apparently do not seem to be greatly influenced by P‐gp in their permeability and consequently also with respect to their extent of GI‐absorption after oral administration, whereas weaker substrates of P‐gp, e.g., talinolol, have clearly shown P‐gp‐related …
Intestinal drug efflux: formulation and food effects
2001
The intestine, primarily regarded as an absorptive organ, is also prepared for the elimination of certain organic acids, bases and neutral compounds depending on their affinity to intestinal carrier systems. Several of the transport systems known to mediate efflux in the major clearing organs--liver and kidney--are also expressed in the intestine. Examples of secretory transporters in the intestine are P-glycoprotein, members of the multidrug resistance associated protein family, breast cancer resistance protein, organic cation transporters and members of the organic anion polypeptide family. In this communication, the P-glycoprotein mediated intestinal secretion of talinolol, a model compo…
Caco‐2 versus Caco‐2/HT29‐MTX Co‐cultured Cell Lines: Permeabilities Via Diffusion, Inside‐ and Outside‐Directed Carrier‐Mediated Transport
2000
Abstract Purpose The objective of this study was a systematic characterization and evaluation of cell culture models based on mixtures of Caco‐2/HT29‐MTX co‐cultures for their use in screening for drug absorption and intestinal permeability in comparison to the properties of the respective mono‐cultures. Methods Co‐cultures of Caco‐2 cells (absorptive‐type) and HT29‐MTX cells (goblet‐type) were set up. Three different co‐cultures (initial seeding ratios Caco‐2/HT29‐MTX: 90/10, 70/30, and 50/50) were grown on permeable filter supports, and monolayers were used for permeability studies with model compounds for paracellular absorption (atenolol, furosemide, H334/75, mannitol, terbutaline), tra…
Effects of controlled-release on the pharmacokinetics and absorption characteristics of a compound undergoing intestinal efflux in humans
2006
Abstract Objective The number of active pharmaceutical ingredients (API) undergoing inhibitable and saturable intestinal efflux is considerable. As a consequence, absorption and bioavailability may depend on the intestinal concentration profile of the drug and may vary as a function of dose and release rate of the drug from the dosage form. The impact of controlled versus immediate-release on the absorption of P-glycoprotein substrates is currently unknown. Thus, the main focus of the present study was a comparison of the pharmacokinetics of the P-gp model substrate talinolol following administration of immediate-release (IR) and controlled-release (CR) tablets to healthy human volunteers w…