scholarly journals Vitamin A Absorption Determined in Rats Using a Plasma Isotope Ratio Method

2020 ◽  
Vol 150 (7) ◽  
pp. 1977-1981 ◽  
Author(s):  
Michael H Green ◽  
Joanne Balmer Green
Keyword(s):  
Vitamin A ◽  
Oral Dose ◽  
Isotope Ratio ◽  
Cholesterol Absorption ◽  
Absorption Efficiency ◽  
Intravenous Dose ◽  
Ratio Method ◽  
Sprague Dawley ◽  
Retinyl Acetate ◽  
Dose Fraction

ABSTRACT Background Better methods are needed for determining vitamin A absorption efficiency. Objective Our objective was to measure vitamin A absorption in rats by adapting a plasma isotope ratio method previously used to determine cholesterol absorption. Methods Male Sprague-Dawley rats [n = 14; 340 ± 16 g (mean ± SD)] received an oral tracer dose of [3H]retinyl acetate in oil plus an intravenous dose of [14C]vitamin A–labeled lymph prepared in a donor rat that had received [14C]retinyl acetate intraduodenally. Blood samples were collected on days 1, 2, 3, 6, 9, and 12, and plasma was analyzed for 3H and 14C; vitamin A absorption was calculated for each sample as (fraction of oral dose/fraction of intravenous dose) × 100. Radioactivity was also measured in feces and urine collected as pools on days 3, 6, 9, and 12 and in liver and remaining carcass on day 12. Results Vitamin A absorption calculated as the plasma isotope ratio was >100% on day 1, 78% ± 5% on day 6, 76% ± 5% on day 9, and 74% ± 5% on day 12; fitting the data to an exponential function plus a constant predicted an absorption of 75% by day 14. Recovery of the oral dose in feces (day 0 to day 6) was low (6.2% ± 0.84%, n = 10) and the mean isotope ratio in day 9–12 urine pool was lower than that in plasma. Conclusions The plasma isotope ratio holds promise for estimating vitamin A absorption, but additional work is needed to determine how long studies need to be and if the doses should be administered simultaneously. For application of this method in humans, artificial chylomicrons labeled with a stable isotope of retinyl acetate could be used for the intravenous dose, with a different isotope required for the oral dose.

scholarly journals Interspecies Comparison of Pharmacokinetics of the Novel Triazole Antifungal Agent SYN-2869 and Its Derivatives

2000 ◽  
Vol 44 (4) ◽  
pp. 910-915 ◽  
Author(s):  
Jehangir K. Khan ◽  
Hashem Montaseri ◽  
Marzena Poglod ◽  
Hai-Zhi Bu ◽  
Zhong Zuo ◽  
...  
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Half Life ◽  
Animal Species ◽  
Intravenous Dose ◽  
Single Intravenous Dose ◽  
Sprague Dawley ◽  
Time Curve ◽  
Toxicological Evaluation ◽  
Significant Difference

ABSTRACT The pharmacokinetics and distribution in tissue of several novel triazole antifungal agents were studied in different animal species in order to select an appropriate lead compound. The purpose of the study was also to determine species differences in pharmacokinetics for SYN azoles to select the most appropriate species for secondary efficacy and toxicological evaluation of the selected compound. SYN-2836, SYN-2869, SYN-2903, and SYN-2921 were rapidly absorbed into the systemic circulation and reached maximum concentrations (C maxs) of 7.31 ± 2.53, 6.29 ± 0.85, 6.16 ± 0.39, and 3.41 ± 0.34 μg/ml, respectively, in BALB/c mice after administration of an oral dose of 50 mg/kg of body weight, with bioavailability being greater than 45% in all mice. The areas under the concentration-time curve from time zero to infinity (AUC0–∞s) after administration of a single intravenous dose of 20 mg/kg to mice varied between 25.0 and 63.6 μg · h/ml. The half-life was in the range of 4.5 to 6 h. In Sprague-Dawley rats there was no significant difference in AUC0–∞ after administration of a single intravenous dose of 20 mg/kg, but on oral administration, the bioavailability of SYN-2836 was extremely low, while that of SYN-2869 was only 14.7%. In New Zealand White rabbits the C max and the time to reach C max for SYN-2836 and SYN-2869 after administration of a single oral dose of 50 mg/kg were similar. There were significant differences in AUC0–∞ and half-life between SYN-2836 and SYN-2869. On the other hand, in beagle dogs theC max and AUC0–∞ of SYN-2836 after administration of a single oral dose of 30 mg/kg were 4.82 ± 1.54 μg/ml and 41.8 ± 15.7 μg · h/ml, respectively, which were threefold higher than those of SYN-2869. The concentrations of the SYN compounds in tissue indicated that the AUC0–∞s of SYN-2836, SYN-2869, SYN-2903, and SYN-2921 in mouse lungs were significantly different from each other. The ratios of the concentrations of the SYN azoles in lungs to those in plasma were also significantly different from those for itraconazole. Among the SYN azoles the highest concentration in the lungs was found for SYN-2869. The higher level of distribution of SYN-2869 into lung tissue was considered to contribute to the potent efficacy in respiratory tract infection models compared with the potency of itraconazole. Significant differences in the pharmacokinetics of these compounds were observed in different animal species, and selection of an animal model for further evaluation was based on results obtained from these studies.

scholarly journals Plasma kinetics of an oral dose of [2H4]retinyl acetate in human subjects with estimated low or high total body stores of vitamin A

1998 ◽  
Vol 68 (1) ◽  
pp. 90-95 ◽  
Author(s):  
M J Haskell ◽  
M A Islam ◽  
G J Handelman ◽  
J M Peerson ◽  
A D Jones ◽  
...  
Keyword(s):  
Vitamin A ◽  
Oral Dose ◽  
Human Subjects ◽  
Retinyl Acetate ◽  
Plasma Kinetics ◽  
Total Body ◽  
Kinetics Of

Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse

2003 ◽  
Vol 285 (3) ◽  
pp. G494-G502 ◽  
Author(s):  
David Q.-H. Wang ◽  
Susumu Tazuma ◽  
David E. Cohen ◽  
Martin C. Carey
Keyword(s):  
Bile Salt ◽  
Bile Acids ◽  
Cholesterol Absorption ◽  
Absorption Efficiency ◽  
Ratio Method ◽  
Susceptible Mouse ◽  
Hydrophobicity Index ◽  
Intestinal Cholesterol Absorption ◽  
Principal Mechanism ◽  
Dual Isotope

We explored the influence of the hydrophilic-hydrophobic balance of a series of natural bile acids on cholesterol absorption in the mouse. Male C57L/J mice were fed standard chow or chow supplemented with 0.5% cholic; chenodeoxycholic; deoxycholic; dehydrocholic; hyocholic; hyodeoxycholic; α-, β-, or ω-muricholic; ursocholic; or ursodeoxycholic acids for 7 days. Biliary bile salts were measured by reverse-phase HPLC, and hydrophobicity indices were estimated by Heuman's method. Cholesterol absorption efficiency was determined by a plasma dual-isotope ratio method. In mice fed chow, natural proportions of tauro-β-muricholate (42 ± 6%) and taurocholate (50 ± 7%) with a hydrophobicity index of -0.35 ± 0.04 produced cholesterol absorption of 37 ± 5%. Because bacterial and especially hepatic biotransformations of specific bile acids occurred, hydrophobicity indices of the resultant bile salt pools differed from fed bile acids. We observed a significant positive correlation between hydrophobicity indices of the bile salt pool and percent cholesterol absorption. The principal mechanism whereby hydrophilic bile acids inhibit cholesterol absorption appears to be diminution of intraluminal micellar cholesterol solubilization. Gene expression of intestinal sterol efflux transporters Abcg5 and Abcg8 was upregulated by feeding cholic acid but not by hydrophilic β-muricholic acid nor by hydrophobic deoxycholic acid. We conclude that the hydrophobicity of the bile salt pool predicts the effects of individual fed bile acids on intestinal cholesterol absorption. Natural α- and β-muricholic acids are the most powerful inhibitors of cholesterol absorption in mice and might act as potent cholesterol-lowering agents for prevention of cholesterol deposition diseases in humans.

Absorption and Conversion of a Single Oral Dose of beta-Carotene in Corn Oil to Vitamin A in Sprague-Dawley Rats with Low Reserve of Vitamin A

2003 ◽  
Vol 73 (4) ◽  
pp. 267-273 ◽  
Author(s):  
Barua
Keyword(s):  
Small Intestine ◽  
Vitamin A ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Corn Oil ◽  
Absorbed Dose ◽  
Beta Carotene ◽  
Retinyl Palmitate ◽  
Sprague Dawley ◽  
Deficient Diet

This study was carried out to determine how much of a single oral dose of beta-carotene in oil is absorbed and how much of the absorbed dose is converted to retinoids in rats having a vitamin A reserve at the lowest end of adequate status. Weanling rats raised on a vitamin A-deficient diet for four weeks were given a single oral dose of either corn oil or beta-carotene dissolved in corn oil (1.86 mumol). Serum, liver, and the entire digestive tract of the rats were analyzed for carotenoids and retinoids. Results showed that 4 hours after dosing, 1.64 mumol (88%) of the dose of beta-carotene was found intact, with 17.6% found in the stomach, 21% in the small intestine, and 49.3% in the large intestine. A total of 0.28 mumol of newly formed retinoids (expressed as retinyl palmitate) was present in serum, liver, and mucosa of small intestine. The results suggest that a single oral dose of beta-carotene might not be an effective way of raising vitamin A status in rats.

scholarly journals Inhibition of .BETA.-sitosterol on intestinal cholesterol absorption in rat using in vivo dual isotope ratio method.

1980 ◽  
Vol 26 (2) ◽  
pp. 183-188 ◽  
Author(s):  
Yoshihiro SHIDOJI ◽  
Makoto WATANABE ◽  
Tsuneyuki OKU ◽  
Yasutoshi MUTO ◽  
Norimasa HOSOYA
Keyword(s):  
Isotope Ratio ◽  
Cholesterol Absorption ◽  
Ratio Method ◽  
Intestinal Cholesterol Absorption ◽  
Dual Isotope

Compartmentation of "Endogenous" and Newly Absorbed Vitamin A in the Rat

1974 ◽  
Vol 52 (3) ◽  
pp. 583-589 ◽  
Author(s):  
D. L. Yeung ◽  
M. J. Veen-Baigent
Keyword(s):  
Vitamin A ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Aqueous Phase ◽  
Dilution Effect ◽  
Fecal Excretion ◽  
Retinyl Acetate ◽  
Per Se ◽  
Retinyl Esters

Urinary and fecal excretion of 3H-labelled metabolites of vitamin A was followed in rats given a single oral dose of 3H-11,12-retinyl acetate (RA), followed 8 days later by a dose of non-labelled RA. The level of radioactivity in urine and feces fell to a more consistently lower level by the 8th day after administration of 3H-RA but no dilution effect was seen 24 h after administration of non-labelled RA. Dilution of 3H-metabolites became gradually evident and was statistically significant 4–6 days after the administration of non-labelled RA. The results are considered to be compatible with the theory that newly absorbed vitamin A does not immediately mix with endogenous vitamin A, but is temporarily metabolized (and stored) in a separate compartment. Plasma aqueous phase contained considerable radioactivity not due to vitamin A per se; it likely represented metabolites prior to excretion. It is doubtful these originated in the liver since all hepatic radioactivity was due to retinol and retinyl esters.

scholarly journals Parameter identifiability and Extended Multiple Studies Analysis of a compartmental model for human vitamin A kinetics: fixing fractional transfer coefficients for the initial steps in the absorptive process

2013 ◽  
Vol 111 (6) ◽  
pp. 1004-1010 ◽  
Author(s):  
Hyunjin Park ◽  
Michael H. Green
Keyword(s):  
Vitamin A ◽  
Simulation Analysis ◽  
Serum Vitamin ◽  
Absorption Efficiency ◽  
Study Data ◽  
Retinol Binding Protein ◽  
Transfer Coefficients ◽  
Retinyl Acetate ◽  
Parameter Identifiability ◽  
Modeling Software

In the existing compartmental models of human vitamin A metabolism, parameters related to the absorption of the isotopic oral dose have not been well identified. We hypothesised that fixing some poorly identified parameters related to vitamin A absorption would improve parameter identifiability and add statistical certainty to such models. In the present study, data for serum vitamin A kinetics in nine subjects given [2H8]retinyl acetate orally and a model with absorption fixed at 75 % were used to test this hypothesis. In addition to absorption efficiency, we fixed two other fractional transfer coefficients: one representing the initial processing of the ingested dose and the other representing the direct secretion of retinol bound to retinol-binding protein (RBP) from enterocytes into the plasma. The Windows version of Simulation, Analysis and Modeling software (WinSAAM) was used to fit serum tracer data v. time for each subject. Then, a population model was generated by WinSAAM's Extended Multiple Studies Analysis. All the parameters had fractional standard deviations < 0·5, and none of the pairs of parameters had a correlation coefficient >0·8 (accepted criteria for well-identified parameters). Similar to the values predicted by the original model, total traced mass for retinol was 1160 (sd 468) μmol, and the time for retinol to appear in the plasma bound to RBP was 31·3 (sd 4·4) h. In conclusion, we suggest that this approach holds promise for advancing compartmental modelling of vitamin A kinetics in humans when the dose must be administered orally.

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