scholarly journals Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase crossover design

2019 ◽  
Vol 110 (5) ◽  
pp. 1148-1167 ◽  
Author(s):  
Maret G Traber ◽  
Scott W Leonard ◽  
Ifechukwude Ebenuwa ◽  
Pierre-Christian Violet ◽  
Yu Wang ◽  
...  
Keyword(s):  
Vitamin E ◽  
Crossover Design ◽  
Pharmacokinetic Parameters ◽  
Apparent Effect ◽  
Blood Samples ◽  
Liquid Meal ◽  
Dual Isotope ◽  
Isotope Technique ◽  
Novel Approaches ◽  
Fractional Absorption

ABSTRACT Background Determining the human vitamin E [α-tocopherol (α-T)] requirement is difficult, and novel approaches to assess α-T absorption and trafficking are needed. Objective We hypothesized that the dual-isotope technique, using 2 deuterium-labeled [intravenous (IV) d6- and oral d3-] α-T, would be effective in determining α-T fractional absorption. Further, defined liquid meal (DLM) fat or fasting would modulate α-T fractional absorption and lipoprotein transport. Methods A 3-phase cr ossover design was used. At 0 h, participants received IV d6-α-T and consumed d3-α-T with a 600-kcal DLM (40% or 0% fat) followed by controlled meals or by the 0% fat DLM, a 12-h fast, and then controlled meals. Blood samples and fecal samples were collected at intervals and analyzed by LC-MS. Pharmacokinetic parameters were calculated from plasma tracer concentrations and enrichments. Fractional absorption was calculated from d3- to d6-α-T areas under the curve, from a novel mathematical model, and from the balance method (oral d3-α-T minus fecal d3-α-T excreted). Results Estimated α-T fractional absorption during the 40% fat intervention was 55% ± 3% (mean ± SEM; n = 10), which was 9% less than during the 0% fat intervention (64% ± 3%, n = 10; P < 0.02). Fasting had no apparent effect (56% ± 3%, n = 7), except it slowed plasma oral d3-α-T appearance. Both balance data and model outcomes confirmed that the DLM fat did not potentiate d3-α-T absorption. During the IV emulsion clearance, HDL rapidly acquired d6-α-T (21 ± 2 nmol/L plasma per minute). During the first 8 h postdosing, triglyceride-rich lipoproteins (TRLs) were preferentially d3-α-T enriched relative to LDL or HDL, showing the TRL precursor role. Conclusions Quantitatively, α-T absorption is not limited by fat absence or by fasting. However, α-T leaves the intestine by a process that is prolonged during fasting and potentiated by eating, suggesting that α-T absorption is highly dependent on chylomicron assembly processes. This trial was registered at clinicaltrials.gov as NCT00862433.

scholarly journals Pharmacokinetics and Relative Bioavailability of Flavonoids between Two Dosage Forms of Gegen-Qinlian-Tang in Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chung-Ping Yu ◽  
Chi-Sheng Shia ◽  
Shang-Yuan Tsai ◽  
Yu-Chi Hou
Keyword(s):  
Relative Bioavailability ◽  
Dosage Forms ◽  
Crossover Design ◽  
Pharmacokinetic Parameters ◽  
Blood Samples ◽  
Scutellariae Radix ◽  
Medicine Prescription ◽  
Chinese Medicine Prescription ◽  
Coptidis Rhizoma ◽  
Predetermined Time

Gegen-Qinlian-Tang (GQT), a popular Chinese medicine prescription, consists of Puerariae Radix, Scutellariae Radix, Coptidis Rhizoma, and Glycyrrhizae Radix. This study investigated the pharmacokinetics of GQT in rats and compared the bioavailability between two dosage forms, that is, traditional decoction (TD) and concentrated powder (CP). Rats were given TD and CP of GQT in a crossover design, and blood samples were withdrawn at predetermined time points. The quantitation methods of ten constituents in two dosage forms of GQT and in serum specimen using HPLC were developed and validated in this study. The pharmacokinetic parameters were calculated using noncompartment model. The results showed that daidzein, baicalein, wogonin, berberine, palmatine, and coptisine were not found in the circulation, whereas the sulfates/glucuronides of daidzein, baicalein, and wogonin were the major forms after oral administration of GQT. Comparison between two dosage forms indicated that theAUC0–tof daidzein sulfates/glucuronides after administration of CP was significantly lower than that of TD by 28.9%, whereas the bioavailabilities of baicalin/baicalein and wogonoside/wogonin were comparable between two dosage forms. In conclusion, the major flavonoids of GQT were extensively metabolized into sulfates/glucuronides and present as the major molecules in the circulation. TD of GQT revealed higher bioavailability of daidzin/daidzein than CP.

scholarly journals Vitamin E catabolism in women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase, nonrandomized crossover study

2020 ◽  
Vol 113 (1) ◽  
pp. 92-103
Author(s):  
Maret G Traber ◽  
Scott W Leonard ◽  
Ifechukwude Ebenuwa ◽  
Pierre-Christian Violet ◽  
Mahtab Niyyati ◽  
...  
Keyword(s):  
Vitamin E ◽  
Crossover Study ◽  
Crossover Design ◽  
Intravenous Dose ◽  
Whole Body ◽  
Fecal Excretion ◽  
Liquid Meal ◽  
Healthy Women

ABSTRACT Background Human vitamin E (α-tocopherol) catabolism is a mechanism for regulating whole-body α-tocopherol. Objectives To determine the roles of the intestine and liver on α-tocopherol catabolism as affected by fat or fasting, 2 deuterium-labeled (intravenous d6- and oral d3-) forms of α-tocopherol were used. Methods Healthy women received intravenous d6-α-tocopherol and consumed d3-α-tocopherol with a 600-kcal defined liquid meal (DLM; 40% or 0% fat, n = 10) followed by controlled meals; or the 0% fat DLM (n = 7) followed by a 12-h fast (0% fat-fast), then controlled meals ≤72 h. The order of the 3-phase crossover design was not randomized and there was no blinding. Samples were analyzed by LC/MS to determine the α-tocopherol catabolites and α-carboxyethyl hydroxychromanol (α-CEHC) in urine, feces, and plasma that were catabolized from administered oral d3- and intravenous d6-α-tocopherols. Results Urinary and plasma d3- and d6-α-CEHC concentrations varied differently with the interventions. Mean ± SEM cumulative urinary d6-α-CEHC derived from the intravenous dose excreted over 72 h during the 40% fat (2.50 ± 0.37 μmol/g creatinine) and 0% fat (2.37 ± 0.37 μmol/g creatinine) interventions were similar, but a ∼50% decrease was observed during the 0% fat-fast (1.05 ± 0.39 μmol/g creatinine) intervention (compared with 0% fat, P = 0.0005). Cumulative urinary d3-α-CEHC excretion was not significantly changed by any intervention. Total urinary and fecal excretion of catabolites accounted for &lt;5% of each of the administered doses. Conclusions Differential catabolism of the intravenous d6-α-tocopherol and oral d3-α-tocopherol doses shows both liver and intestine have roles in α-tocopherol catabolism. During the 40% fat intervention, &gt;90% of urinary d3-α-CEHC excretion was estimated to be liver-derived, whereas during fasting &lt;50% was from the liver with the remainder from the intestine, suggesting that there was increased intestinal α-tocopherol catabolism while d3-α-tocopherol was retained in the intestine in the absence of adequate fat/food for α-tocopherol absorption. This trial was registered at clinicaltrials.gov as NCT00862433.

Effects of indirect exposure of mice pups to endosulfan via their dams during gestation and lactation periods and the ameliorative effect of vitamin E

2013 ◽  
Vol 33 (9) ◽  
pp. 911-927 ◽  
Author(s):  
SA Mansour ◽  
DA Mohamed ◽  
L Gamet-Payrastre
Keyword(s):  
Vitamin E ◽  
Low Dose ◽  
Dietary Exposure ◽  
Oral Vitamin ◽  
Blood Samples ◽  
Oral Supplementation ◽  
Maximum Value ◽  
Indirect Exposure ◽  
Ameliorative Effect ◽  
Butyryl Cholinesterase

During gestation and lactation, the experimental mice dams received one of the following treatments: (a) diet free of pesticide; (b) diet enriched with endosulfan (END); 30.0 µg kg−1; (c) diet free of pesticide + oral vitamin E (α-tocopherol; 200 mg kg−1 per mouse); and (d) diet enriched with END (30.0 µg kg−1) + oral vitamin E (200 mg kg−1 per mouse). At weaning, pups and dams were killed, and selected organs as well as blood samples were collected for analyses. Compared with the control results, END induced alteration in a number of biochemical and histopathological parameters either in the dams or their offspring. The ameliorative effect of vitamin E to superoxide dismutase based on the “ameliorative index (AI)” for mothers and pups was 0.84 and 0.72, respectively. The AI for malondialdehyde reached a maximum value of nearly equal to 1.0 for dams or pups. For butyryl cholinesterase, the AI was 0.90 and 0.94 for dams and pups, respectively. In conclusion, a dietary exposure during gestation and lactation to low dose of END caused significant changes in the mother but also in the weaned animals that had not been directly exposed to this pesticide. These biological and histological alterations could be reversed to a great extent by oral supplementation of vitamin E.

Adhesion of Malassezia pachydermatis of different growth type to canine epithelial cells

2014 ◽  
Vol 17 (2) ◽  
pp. 365-366 ◽  
Author(s):  
M. Florek ◽  
J. Król ◽  
Z. Staroniewicz ◽  
B. Bażanów
Keyword(s):  
Vitamin E ◽  
Epithelial Cells ◽  
Glutathione Peroxidase ◽  
Dairy Cows ◽  
Clinical Mastitis ◽  
Control Group ◽  
Growth Type ◽  
Malassezia Pachydermatis ◽  
Blood Samples ◽  
Experimental Group

Abstract This study focuses on the effect of parenteral administration of Selenium (Se) and vitamin E on concentration of Se in plasma and the activity of glutathione peroxidase (GPx) in the blood of dairy cows during peripartal period and their effect on the reduction of clinical mastitis. From a 220 individuals Holstein herd in a two-four lactation-gestation cycle the control group (C), 1st (D1) and 2nd (D2) experimental group were selected. Every group consisted of 15 cows in the last phase of the pregnancy. All cows were fed with the diet containing 0.1 mg of Se per kg/DM. The blood samples from vena jugularis were collected approximately 21 days before calving (control sampling), 3 days, 12 days and 21 days after calving. On the day of control sampling and 12 days before calving in D1 group, cows were injected subcutaneously in the sprescapular region with preparation Selevit inj. a.u.v. at the doses of 48.4 mg/head of Se, and 550 IU/head of α-Tocoferol (α-Toc). In D2 group, cows were injected by the same preparation only on 21th day before calving with the same doses of Se and α-Toc. The increase in the concentration of Se in the plasma and activity GPx in blood in D1 group on the 3rd day and 12th day after calving were determined. Increase in plasmatic concentrations α-Toc on 3rd day after calving and reduction of occurrence of clinical mastitis (13.3%) as compared with control group were found

scholarly journals Effects of Valproic Acid Coadministration on Plasma Efavirenz and Lopinavir Concentrations in Human Immunodeficiency Virus-Infected Adults

2004 ◽  
Vol 48 (11) ◽  
pp. 4328-4331 ◽  
Author(s):  
Robert DiCenzo ◽  
Derick Peterson ◽  
Kim Cruttenden ◽  
Gene Morse ◽  
Garret Riggs ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Valproic Acid ◽  
Geometric Mean ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Blood Samples ◽  
Immunodeficiency Virus ◽  
Before And After ◽  
Trough Concentrations ◽  
Hiv 1

ABSTRACT Valproic acid (VPA) has the potential to benefit patients suffering from human immunodeficiency virus (HIV)-associated cognitive impairment. The purpose of this study was to determine if VPA affects the plasma concentration of efavirenz (EFV) or lopinavir. HIV type 1 (HIV-1)-infected patients receiving EFV or lopinavir-ritonavir (LPV/r) had 9 or 10 blood samples drawn over 8 to 24 h of a dosing interval at steady state before and after receiving 250 mg of VPA twice daily for 7 days. VPA blood samples drawn before (C 0) and 8 h after the morning dose (8 h) were compared to blood samples from a group of HIV-1-infected subjects who were taking either combined nucleoside reverse transcriptase inhibitors alone or had discontinued antiretroviral therapy. Pharmacokinetic parameters were calculated by noncompartmental analysis, and tests of bioequivalence were based on 90% confidence intervals (CIs) for ratios or differences. The geometric mean ratio (GMR) (90% CI) of the areas under the concentration-time curve from 0 to 24 h (AUC0-24s) of EFV (n = 11) with and without VPA was 1.00 (0.85, 1.17). The GMR (90% CI) of the AUC0-8s of LPV (n = 8) with and without VPA was 1.38 (0.98, 1.94). The differences (90% CI) in mean C 0 and 8-h VPA concentrations versus the control (n = 11) were −1.0 (−9.4, 7.4) μg/ml and −2.1 (−11.1, 6.9) μg/ml for EFV (n = 10) and −5.0 (−13.2, 3.3) μg/ml and −6.7 (−17.6, 4.2) μg/ml for LPV/r (n = 11), respectively. EFV administration alone is bioequivalent to EFV and VPA coadministration. LPV concentrations tended to be higher when the drug was combined with VPA. Results of VPA comparisons fail to raise concern that coadministration with EFV or LPV/r will significantly influence trough concentrations of VPA.

A comparison of the efficacy and pharmacokinetics of ivermectin after spring and autumn treatments against Cyathostominae in horses

2015 ◽  
Vol 18 (2) ◽  
pp. 371-377 ◽  
Author(s):  
R. Sokół ◽  
M. Raś-Noryńska ◽  
M. Michalczyk ◽  
A. Jasiecka ◽  
H. Ziółkowski ◽  
...  
Keyword(s):  
High Pressure ◽  
Liquid Chromatography ◽  
Blood Plasma ◽  
Drug Administration ◽  
High Pressure Liquid Chromatography ◽  
Drug Absorption ◽  
Pharmacokinetic Parameters ◽  
Blood Samples ◽  
Fecal Samples ◽  
Single Bolus

Abstract The aim of the present study was to determine the efficacy of ivermectin against Cyathostominae infections and to describe the drug’s pharmacokinetic parameters during two seasonal deworming treatments in horses. The study was performed on warm-blooded mares aged 3-12 years weighing 450-550 kg. A single bolus of an oral paste formulation of ivermectin was administered at a dose of 0.2 mg/kg BW in spring and autumn. Fecal samples were tested before treatment and 1, 2, 3, 4, 6, 10, 20, 30, 40, 50, 60, 75 days after treatment. Ivermectin concentrations in blood samples collected before treatment, 0.5, 1, 2, 3, 4, 6, 12, 24, 36 and 48 hours after treatment, and 3, 4, 6, 8, 10, 15, 20, 25, 30, 40, 50, 60 and 75 days after drug administration were determined by high pressure liquid chromatography. Drug absorption was significantly (p<0.05) slower (tmax: 21.89±11.43 h) in autumn than in spring (tmax: 9.78±8.97 h). Maximum concentrations (Cmax) of ivermectin in the blood plasma of individual horses (8.40-43.08 ng/ml) were observed 2-24 h after drug administration during the spring treatment and 2-36 h (6.43-24.86 ng/ml) after administration during the autumn treatment. Significantly higher (p<0.05) ivermectin concentrations were found during the first 4 hours after administration in spring in comparison with those determined after the autumn treatment. The administration of the recommended dose of ivermectin resulted in 100% elimination of parasitic eggs from feces in spring and autumn treatment.

scholarly journals Vitamin e-loaded membrane dialyzers reduce hemodialysis inflammaging

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Vincenzo Sepe ◽  
Marilena Gregorini ◽  
Teresa Rampino ◽  
Pasquale Esposito ◽  
Rosanna Coppo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vitamin E ◽  
Serum Levels ◽  
Hemodialysis Patients ◽  
Control Group ◽  
Low Grade ◽  
Oxide Formation ◽  
Blood Samples ◽  
Indoleamine 2,3 Dioxygenase ◽  
Nitric Oxide Formation

Abstract Background Inflammaging is a persistent, low−grade, sterile, nonresolving inflammatory state, associated with the senescence of the immune system. Such condition downregulates both innate and adaptive immune responses during chronic disorders as type II diabetes, cancer and hemodialysis, accounting for their susceptibility to infections, malignancy and resistance to vaccination. Aim of this study was to investigate hemodialysis inflammaging, by evaluating changes of several hemodialysis treatments on indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation. Methods We conducted a randomized controlled observational crossover trial. Eighteen hemodialysis patients were treated with 3 different hemodialysis procedures respectively: 1) Low−flux bicarbonate hemodialysis, 2) Low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, and 3) Hemodialfitration. The control group consisted of 14 hospital staff healthy volunteers. Blood samples were collected from all 18 hemodialysis patients just after the long interdialytic interval, at the end of each hemodialysis treatment period. Results Hemodialysis kynurenine and kynurenine/L − tryptophan blood ratio levels were significantly higher, when compared to the control group, indicating an increased indoleamine 2,3-dioxygenase-1 activity in hemodialysis patients. At the end of the low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers period, L − tryptophan serum levels remained unchanged vs both low−flux bicarbonate hemodialysis and hemodialfitration. Kynurenine levels instead decreased, resulting in a significant reduction of kynurenine/L − tryptophan blood ratio and indoleamine 2,3-dioxygenase-1 activity, when matched to both low−flux bicarbonate hemodialysis and HDF respectively. Serum nitric oxide control group levels, were significantly lower when compared to all hemodialysis patient groups. Interestingly, low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers nitric oxide serum levels from venous line blood samples taken 60 min after starting the hemodialysis session were significantly lower vs serum taken simultaneously from the arterial blood line. Conclusions The treatment with more biocompatible hemodialysis procedure as low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers, reduced indoleamine 2,3-dioxygenase-1 activity and nitric oxide formation when compared to both low−flux bicarbonate hemodialysis and hemodialfitration. These data suggest that low−flux bicarbonate hemodialysis with vitamin E − loaded dialyzers lowering hemodialysis inflammaging, could be associated to changes of proinflammatory signalling a regulated molecular level. Trial registration NCT Number: NCT02981992; Other Study ID Numbers: 20100014090. First submitted: November 26, 2016. First posted: December 5, 2016. Last Update Posted: December 5, 2016.

scholarly journals Herb-Drug Interaction: Effects of Relinqing® Granule on the Pharmacokinetics of Ciprofloxacin, Sulfamethoxazole, and Trimethoprim in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Yuan Lu ◽  
ZiPeng Gong ◽  
YuMin Xie ◽  
Jie Pan ◽  
Jia Sun ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Pharmacokinetic Parameters ◽  
Control Group ◽  
Urinary System ◽  
Blood Samples ◽  
Sd Rats ◽  
Chinese Patent ◽  
Group 2 ◽  
And Control ◽  
Group 1

Relinqing granule (RLQ) is the best-selling Chinese patent drug for treatment of urinary system diseases. In this study, the effects of RLQ on the pharmacokinetics of ciprofloxacin, sulfamethoxazole, and trimethoprim in SD rats were investigated. Rats were randomly divided into control group 1, control group 2, RLQ group 1, and RLQ group 2. RLQ group 1 and RLQ group 2 were treated orally with RLQ for 7 days, and rats were treated with the same volume of water in control group 1 and control group 2. Then, RLQ group 1 and control group 1 were given intragastrically ciprofloxacin on day 8, while RLQ group 2 and control group 2 were given intragastrically sulfamethoxazole and trimethoprim on day 8. Blood samples were collected and determined. There was no significant influence of pharmacokinetic parameters of trimethoprim on two groups. But some pharmacokinetic parameters of ciprofloxacin and sulfamethoxazole in RLQ pretreated rats were evidently altered (P < 0.05), which indicated that absorption of ciprofloxacin and sulfamethoxazole in RLQ pretreated rats was significantly affected. It indicated the coadministration of RLQ would have an influence on the efficacy of ciprofloxacin and sulfamethoxazole, and the doses of ciprofloxacin tablet and compound sulfamethoxazole tablet need adjustment.

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