Metabolism of progesterone, 17-hydroxyprogesterone and deoxycorticosterone by human small intestine in vitro

Nienstedt, Walter; Ojanotko, A.; Toivonen, Heikki

doi:10.1016/0022-4731(80)90053-9

Cited by 14 publications

(4 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hence, there is a need for simplified in vitro screening that results in the emergence of an in vitro lipolysis model. The dynamic in vitro lipolysis model offers a good mockup of the in vivo lipid digestion process and achieves good in vitro–in vivo correlation (IVIVC) when predicting compound bioavailability. ,− …”

Section: Results and Discussionmentioning

confidence: 99%

Effect of a Labile Methyl Donor on the Transformation of 5-Demethyltangeretin and the Related Implication on Bioactivity

Ting

Pan

et al. 2013

J. Agric. Food Chem.

View full text Add to dashboard Cite

Polymethoxyflavones (PMFs) belong to a subgroup of flavonoids that particularly exist in the peels of citrus fruits. Despite their many health-beneficial biofunctionalities, the lipophilic nature of PMFs limits their water solubility and oral bioavailability. To investigate the effect of the delivery system on the improvement of PMF bioavailibility, a lecithin-based emulsion was formulated for the delivery of two PMF compounds, tangeretin and 5-demethyltangeretin. While the emulsion system improved the digestion kinetics and the total solubilized PMF concentrations in in vitro lipolysis studies, the concentration of 5-demethyltangeretin decreased due to chemical transformation to its permethoxylated counterpart, tangeretin. The emulsifier lecithin used in this emulsion formulation contained a choline headgroup as a labile methyl group donor. The presence of a methyl donor potentially caused the transformation of 5-demethyltangeretin and reduced its anti-cancer-cell-proliferation activities. Moreover, this is the first report in the literature of the transformation from 5-demethyltangeretin to tangeretin in a lecithin-based emulsion during lipolysis, and the mechanism underlying this phenomenon has also been proposed for the first time.

show abstract

Section: Results and Discussionmentioning

confidence: 99%

Effect of a Labile Methyl Donor on the Transformation of 5-Demethyltangeretin and the Related Implication on Bioactivity

Ting

Pan

et al. 2013

J. Agric. Food Chem.

View full text Add to dashboard Cite

show abstract

“…In this study, progesterone was selected as a model lipophilic compound (log P = 4.0) with low oral bioavailability (less than 5%) due to poor water solubility and significant pre-systemic oxidative metabolism, where more than 50% of progesterone dose have been shown to undergo pre-systemic metabolism in the gut wall (10,11). It has been shown before that certain lipid based formulations may improve the oral bioavailability of this hormone (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…Progesterone reflects low oral bioavailability due to poor solubility and significant pre systemic metabolism, when more than 50% of progesterone dose undergo pre-systemic metabolism in the gut wall (10,11). Vitamin D 3 represents lipophilic compounds that are transported mainly via the lymphatic system (12).…”

Section: Introductionmentioning

confidence: 99%

Use of a Dynamic in Vitro Lipolysis Model to Rationalize Oral Formulation Development for Poor Water Soluble Drugs: Correlation with in Vivo Data and the Relationship to Intra-Enterocyte Processes in Rats

2006

View full text Add to dashboard Cite

show abstract

“…Mannitol and PEG are commonly used as nonmetabolizable markers for paracellular transport. Didanosine, 24,29 formycin B, 30,31 AZT, 32 proline, 33 phenylalanine, 34 and progesterone 35 have been reported as either stable or minimally metabolized in intestinal preparations.…”

Section: Materialssmentioning

confidence: 98%

Influence of the Microporous Substratum and Hydrodynamics on Resistances to Drug Transport in Cell Culture Systems: Calculation of Intrinsic Transport Parameters

Sinko

1997

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Although cell culture models are increasingly used to study drug transport and metabolism, the influence of the substratum on the transport properties of the cell monolayer has not been studied in great detail. Furthermore, the use of effective (or apparent) permeabilities (Peff) assumes that the contribution of the microporous filter substratum and the aqueous boundary layer (ABL) to transport are negligible or are at least constant for a series of drugs. In the present study, the permeabilities of the substratum, ABL, and monolayer were obtained for a series of compounds at variable flow rates in side-by-side diffusion chambers. Comparisons of transport properties were made between cell monolayers grown on substrata made of polycarbonate (PC) and polyester (PE). All paracellular markers demonstrated a reduction in permeability and a corresponding increase in transepithelial electrical resistance (TEER) through PE-grown monolayers. The permeabilities of two carrier-mediated compounds, phenylalanine and proline, were 55% higher and 48% lower through PE-grown monolayers than through the PC-grown monolayers, respectively. The resistance to progesterone transport attributed to the PE and PC filters was large (71% and 27% of total resistance, respectively) at a flow rate of 20 mL/min, indicating that the monolayer was not the rate-limiting transport barrier. Therefore, for highly permeable compounds, reporting Peff has limited value since it is an indicator of the transport properties of the substratum rather than of the monolayer. These results demonstrate that substratum properties (e.g., membrane composition, pore size, etc.) significantly affect the barrier properties of the Caco-2 cell monolayer. The most probable mechanism is by the modulation of the functional expression of nutrient and ion transporters resulting in variable transcellular and paracellular transport properties. These results further demonstrate the importance of calculating intrinsic membrane transport parameters if the monolayer is not maintained as the rate-determining barrier in the transport experiment. Using higher flow rates and higher porosity substrata supports may help maintain the monolayer as the rate-limiting transport barrier.

show abstract

Metabolism of progesterone, 17-hydroxyprogesterone and deoxycorticosterone by human small intestine in vitro

Cited by 14 publications

References 7 publications

Effect of a Labile Methyl Donor on the Transformation of 5-Demethyltangeretin and the Related Implication on Bioactivity

Effect of a Labile Methyl Donor on the Transformation of 5-Demethyltangeretin and the Related Implication on Bioactivity

Use of a Dynamic in Vitro Lipolysis Model to Rationalize Oral Formulation Development for Poor Water Soluble Drugs: Correlation with in Vivo Data and the Relationship to Intra-Enterocyte Processes in Rats

Influence of the Microporous Substratum and Hydrodynamics on Resistances to Drug Transport in Cell Culture Systems: Calculation of Intrinsic Transport Parameters

Contact Info

Product

Resources

About