Postprandial Evolution in Composition and Characteristics of Human Duodenal Fluids in Different Nutritional States

Clarysse, Sarah; Tack, Jan; Lammert, Frank; Duchateau, Guus; Reppas, Christos; Augustijns, Patrick

doi:10.1002/jps.21502

Cited by 117 publications

(147 citation statements)

References 40 publications

(75 reference statements)

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“…This is in agreement with a recent study (17). Also, very recently, by using a gas chromatography method, it has been reported that cholate and chenodeoxycholate constitute most of the total bile acid pool in the fed duodenum (18). However, the relevant method does not allow distinguishing between conjugated and unconjugated bile acids.…”

Section: Methods Validationsupporting

confidence: 91%

“…Gas chromatography has recently been applied for quantifying bile acids in the duodenum (18). Issues with gas chromatography include the need for silylation (i.e., the need for appropriate sample preparation procedures) and also the fact that conjugated bile acids cannot be distinguished from nonconjugated bile acids (18).…”

Section: Discussionmentioning

confidence: 99%

“…Issues with gas chromatography include the need for silylation (i.e., the need for appropriate sample preparation procedures) and also the fact that conjugated bile acids cannot be distinguished from nonconjugated bile acids (18). Finally, an LC-tandem mass spectrometry method, originally developed for assaying individual bile acids in human serum (22), has been applied for the determination of intraduodenal bile acid levels (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Using an HPLC-ELSD method (17) the mean 6 SD total bile acid level in the fed jejunum was estimated to be 8 6 0.1 mM. Very recently, Clarysse et al (18), using a gas chromatography method, reported that within 30 min after meal administration, individual intraduodenal concentrations of total bile acids ranged …”

Section: Methods Validationmentioning

confidence: 99%

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Determination of intralumenal individual bile acids by HPLC with charged aerosol detection

Vertzoni

Archontaki

Reppas

2008

Journal of Lipid Research

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An isocratic HPLC charged aerosol detector (CAD) method was developed, validated, and applied for the determination of individual bile acids in human gastric and duodenal aspirates. The method requires a low volume of aspirates (50-100 ml) and minimal sample pretreatment. A Hypersil BDS RP-C 18 column (250 3 4.6 mm, 5 mm particle size) was equilibrated with a mobile phase composed of methanol-[ammoniun formate 20 mM, formic acid 0.5%, triethylamine 0.2% (pH 3)] 67:33 v/v. Its flow rate was 1 ml/min. The elution times for taurocholate, glycocholate, taurochenodeoxycholate, ursodeoxycholate, glycochenodeoxycholate, cholate, and glycodeoxycholate were approximately 9.9, 16.2, 18.2, 21.3, 31.6, 34.5, and 38.5 min, respectively. Calibration curves in the mobile phase were constructed in the concentration range of 0.5-500 mM. Limits of detection and quantification were in the range of 0.07-0.60 mM and 0.20-1.80 mM, respectively. This method was applied first, in gastric aspirates collected in the fasted state, in which bile acid presence is minimal and, second, in duodenal aspirates collected in the fed state, in which a large number of potentially interfering compounds exists. Intra-day relative standard deviation in fasted gastric aspirates and in fed duodenal aspirates was less than 2.2% and 6.0%, respectively.-Vertzoni, M., H. Archontaki, and C. Reppas. Determination of intralumenal individual bile acids by HPLC with charged aerosol detection. J. Lipid Res. 2008Res. . 49: 2690Res. -2695

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Section: Methods Validationsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methods Validationmentioning

confidence: 99%

See 2 more Smart Citations

Determination of intralumenal individual bile acids by HPLC with charged aerosol detection

Vertzoni

Archontaki

Reppas

2008

Journal of Lipid Research

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“…We were surprised to find that the solubility in FeSSIF (321 Ϯ 18 M) was lower than that in FaSSIF. In view of the recently reported high intra-and interindividual variability of the solubilizing capacity of HIF (Clarysse et al, 2009), the reported values of the solubility values in HIF should be considered as an estimate of the intraluminal concentration. The observed solubility values suggest that, after oral administration, DRV can be present at high concentrations in the intestinal lumen.…”

Section: Resultsmentioning

confidence: 99%

In Situ Intestinal Perfusion in Knockout Mice Demonstrates Inhibition of Intestinal P-Glycoprotein by Ritonavir Causing Increased Darunavir Absorption

Holmstock

Mols²,

Annaert³

et al. 2010

Drug Metab Dispos

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ABSTRACT:Darunavir is a second-generation protease inhibitor designed to have antiviral efficacy against HIV-1 with multiple resistance mutations to protease inhibitors. It is always coadministered with a subtherapeutic dose of ritonavir. It has been shown that darunavir and ritonavir are substrates of P-glycoprotein (P-gp). We explored the contribution of P-gp to the transport characteristics of darunavir (up to 100 M) using Caco-2 monolayers and the recently developed in situ intestinal perfusion technique using wild-type and mdr1a/1b(؊/؊) mice. We observed that, in vitro, P-gp has a modulatory effect on the absorption of darunavir, even at a concentration of 100 M (efflux ratio ‫؍‬ 25). Simulated intestinal fluids partially inhibited P-gp functionality, which was further inhibited by adding the P-gp inhibitors verapamil, 6-[(2S,4R,6E)-4-methyl-2-(methylamino)-3-oxo-6-octenoic acid]cyclosporine D (PSC833), N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl) ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918), or ritonavir. Using the in situ intestinal perfusion technique, we demonstrated that coperfusion with ritonavir resulted in a similar apparent permeability coefficient to that observed using P-gp knockout mice, which was 2.7-fold higher than in control mice. We conclude that, in mice, even at a relevant intraluminal concentration of darunavir, P-gp has a modulatory effect on the absorption of darunavir. However, this P-gp-mediated darunavir transport is inhibited when it is combined with ritonavir. IntroductionThe combination of multiple antiretroviral drugs with different modes of action (highly active antiretroviral therapy) has contributed to a spectacular progress in the fight against HIV (Hammer et al., 2008). The standard regimen for newly diagnosed patients usually includes two nucleoside reverse transcriptase inhibitors combined with either a protease inhibitor [boosted with ritonavir (RTV)] or a non-nucleoside reverse transcriptase inhibitor. Darunavir [(DRV) Prezista; Tibotec Pharmaceuticals, Cork, Ireland] is a second-generation protease inhibitor (PI) designed to have antiviral efficacy against HIV-1 with multiple resistance mutations to protease inhibitors (Busse and Penzak, 2007;Tremblay, 2008). RTV is always coadministered in a subtherapeutic dose as a pharmacokinetic booster of DRV.In vitro and in vivo studies have demonstrated that all HIV PI are high-affinity substrates for P-glycoprotein [(P-gp) multidrug resistance 1 (MDR1)], which can significantly influence the disposition of antiretroviral drugs (Kis et al., 2009). P-gp is widely distributed with a high level of expression in the small intestine, liver, kidney, and brain (Ho and Kim, 2005). Presently, however, there is still uncertainty about the role of intestinal P-gp in vivo. It is not sure whether P-gp plays a pivotal role as a biochemical barrier for compounds at concentrations relevant for the intraluminal environment, because of a possible saturation of the efflux system. In addition, it has b...

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et al. 2021

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Postprandial Evolution in Composition and Characteristics of Human Duodenal Fluids in Different Nutritional States

Cited by 117 publications

References 40 publications

Determination of intralumenal individual bile acids by HPLC with charged aerosol detection

Determination of intralumenal individual bile acids by HPLC with charged aerosol detection

In Situ Intestinal Perfusion in Knockout Mice Demonstrates Inhibition of Intestinal P-Glycoprotein by Ritonavir Causing Increased Darunavir Absorption

Impact of Anatomy and Physiology

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