A Single Ascending Dose Study of Epigallocatechin Gallate in Healthy Volunteers

2003 ◽  
Vol 31 (2) ◽  
pp. 88-101 ◽  
Author(s):  
U Ullmann ◽  
J Haller ◽  
JP Decourt ◽  
N Girault ◽  
J Girault ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Time Course ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Epigallocatechin Gallate ◽  
Controlled Study ◽  
Maximum Plasma ◽  
Double Blind ◽  
The Mean ◽  
Oral Doses

This randomized, double-blind, placebo-controlled study assessed the safety, tolerability and plasma kinetic behaviour of single oral doses of 94% pure crystalline bulk epigallocatechin gallate (EGCG) under fasting conditions in 60 healthy male volunteers. In each group of 10 subjects, eight received oral EGCG in single doses of 50 mg, 100 mg, 200 mg, 400 mg, 800 mg or 1600 mg, and two received placebo. Blood samples were taken at intervals until 26 h later. The area under the concentration-time curve from 0 h to infinity (AUC(0–∞)), the maximum plasma concentration ( Cmax) of EGCG, the time taken to reach the maximum concentration ( Tmax), and the terminal elimination half-life ( t1/2z) of EGCG were determined. Safety and tolerability were assessed. In each dosage group, the kinetic profile revealed rapid absorption with a one-peak plasma concentration versus time course, followed by a multiphasic decrease consisting of a distribution phase and an elimination phase. The mean AUC(0– ∞) of total EGCG varied between 442 and 10368 ng·h/ml. The according mean Cmax values ranged from 130 to 3392 ng/ml and were observed after 1.3–2.2 h. The mean t1/2z values were seen between 1.9 and 4.6 h. Single oral doses of EGCG up to 1600 mg were safe and very well tolerated.

Safety, Tolerability, and Pharmacokinetics of Sumatriptan in Healthy Subjects Following Ascending Single Intranasal Doses and Multiple Intranasal Doses

Cephalalgia ◽  
1997 ◽  
Vol 17 (4) ◽  
pp. 541-550 ◽  
Author(s):  
KHP Moore ◽  
EK Hussey ◽  
S Shaw ◽  
E Fuseau ◽  
C Duquesnoy ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Adverse Events ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Dose Range ◽  
Maximum Plasma ◽  
Multiple Doses ◽  
To Receive ◽  
Intranasal Spray ◽  
Female Subjects

The delivery of sumatriptan doses intranasally could add greater flexibility in the treatment of migraine than is possible with the currently available subcutaneous and oral sumatriptan preparations. Two independent double-blind, randomized, placebo-controlled clinical studies were conducted to evaluate the safety, tolerability and pharmacokinetics of intranasally administered sumatriptan following ascending single doses (three different dose levels) and multiple doses. In the four-way crossover, ascending-dose study, 20 healthy female subjects were randomized to receive on separate occasions single intranasal spray doses of 5, 10, or 20 mg sumatriptan (as the hemisulphate salt) or placebo into one nostril. Adverse events were mild and consisted mainly of bitter taste at the back of the throat and events typical of sumatriptan administered by other routes (headache, lightheadedness and tingling). Area under the plasma sumatriptan concentration versus time curve (AUC) and peak plasma concentration (Cmax) increased with the dose. Dose proportionality was demonstrated between 5 and 10 mg but not across the dose range 5–20 mg. Time to maximum plasma concentration (tmax) was variable due to multiple peaking. The elimination half-life (t1/2), approximately 2 h, was unaffected by the magnitude of dose. In the two-period, multiple-dose, crossover study, 12 healthy adult male and female subjects were randomized to receive either sumatriptan hemisulphate 20 mg or placebo, administered intranasally as a spray three times a day for 4 days, The two dosing periods were separated by 3 to 14 days. Multiple doses of sumatriptan were well tolerated, with no serious adverse events occurring or withdrawals due to adverse events. All patients reported a mild to moderate drug-related disturbance of taste. Nasal examinations remained normal, and olfactory function was unaffected. The AUC over the first 8 h following dosing (AUC8) and fraction of the dose excreted in the urine (fe; 6.2% vs 3.6%) were similar on Days 1 and 4. Day 4 values were significantly higher (p0.05) for Cmax (16.9 ng/ml vs 13.1 ng/ml), renal clearance (Clr; 19.0 l/h vs 14.2 l/h), and t1/2 (2.18 h vs 1.93 h), and shorter for tmax (0.88 h vs 1.75 h). Some accumulation (22%) occurred over the 4 days of dosing. Serum concentrations of the pharmacologically inactive indole acetic acid metabolite of sumatriptan were fourfold to fivefold higher than corresponding sumatriptan concentrations. Overall, these studies show the sumatriptan intranasal spray formulation is well tolerated, allows rapid absorption of sumatriptan, and results in only a clinically insignificant degree of sumatriptan accumulation upon repeated dosing.

Trigeminal Neuralgia: Time Course of Pain in Relation to Carbamazepine Dosing

Cephalalgia ◽  
1981 ◽  
Vol 1 (2) ◽  
pp. 91-97 ◽  
Author(s):  
Torbjörn Tomson ◽  
Karl Ekbom
Keyword(s):  
Plasma Concentration ◽  
Trigeminal Neuralgia ◽  
Time Course ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Plasma Concentrations ◽  
Significant Drop ◽  
Idiopathic Trigeminal Neuralgia ◽  
Full Effect ◽  
Pain Distribution

Eight in-patients with idiopathic trigeminal neuralgia (TN) were studied while receiving carbamazepine (CBZ) treatment. The aim was to study diurnal pain distribution, its relation to CBZ dosing and plasma concentration and the effect of decreasing the dose. All pain attacks were registered by the patients at three-hour intervals. CBZ was given b.i.d. in a single blind manner with the patient unaware of dose and dose changes. Plasma concentrations of CBZ were followed every fourth hour during a period of altogether sixteen dosage intervals. The diurnal pain distribution revealed marked intra-individual similarities with pain-free nights and a significant drop in pain during mid-day hours. The latter coincided in time with the peak plasma concentration of CBZ, thus indicating an effect of plasma concentration fluctuations on pain relief. Shorter dosage intervals might therefore be beneficial in problem cases. A significant increase in pain was detected within six to nine hours after a dose reduction, whereas the full effect of the dose change seemed to be established only after one day.

Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Preeti D. Kulkarni ◽  
Neena D. Damle ◽  
Lal Hingorani ◽  
Vaidhun H. Bhaskar ◽  
Minal R. Ghante ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Oral Bioavailability ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Maximum Plasma ◽  
Boswellic Acid ◽  
Healthy Human ◽  
Boswellia Serrata ◽  
Solid Lipid ◽  
Human Volunteers

Abstract Objectives The anti-inflammatory activity of Boswellia serrata extracts (BSE) is well known. BSE comprises boswellic acids (BA) such as 3-O-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) as major constituents. One of the limitations of BAs is their poor oral bioavailability. The aim of the study was to prepare solid lipid particles of Boswellia serrata extract (SLBSP) to enhance the bioavailability of BAs. Methods The pharmacokinetic profile of BAs was studied in 10 healthy human volunteers following a single oral dose of 333 mg of SLBSP. Pharmacokinetic blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h post drug administration. Plasma KBA and AKBA levels were measured using a validated LC-MS/MS method. Pharmacokinetics parameters were estimated using Pheonix WinNonlin (Build 6.4.0.768) software. Results Ten healthy human volunteers were included and peak plasma concentration was achieved in 1.5 and 2.3 h for AKBA and KBA respectively. Maximum plasma concentration (C max) was 8.04 ± 1.67 ng/mL for AKBA and 23.83 ± 4.41 ng/mL for KBA whereas the corresponding area under the concentration-time curve (AUC) was 136.7 ± 56.77 ng/mL*h and 165.7 ± 24.5 ng/mL*h respectively. The elimination half-life (t 1/2) of AKBA and KBA was 6.8 ± 3.0 h and 2.45 ± 0.3 h respectively. Conclusions The SLBSP formulation of BSE showed enhanced oral bioavailability of BAs compared with historically reported data of unformulated BSE.

scholarly journals Comparative bioavailability study of phenytoin in healthy Nepalese volunteers

2019 ◽  
Vol 9 (1-s) ◽  
pp. 144-147
Author(s):  
DIllisher Rai ◽  
Gajendra Prasad Rauniar
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
P Value ◽  
Maximum Plasma ◽  
Time Curve ◽  
Oral Tablet ◽  
Concentration Time ◽  
Plasma Concentration Time Curve

Our study aimed to assess and compare the bioavailability of Eptoin 100 mg and Epileptin 100mg tablets in Nepalese healthy volunteers. A randomized, two-treatment cross-over study with two weeks’ wash-out period was conducted in 12 healthy non-smoker and non-alcoholic Nepalese male volunteers over a period of 6 months in the department of Clinical Pharmacology and Therapeutic at B. P. Koirala Institute of Health Sciences, Dharan, Nepal after approval from the Institutional Review Committee. The participants were randomized using sealed envelope system and received a single 100 mg oral tablet of either of the formulations with a two week washout period. Blood samples were collected predose and at regular intervals postdose upto 72 hours. Plasma phenytoin levels were estimated by reverse phase high performance liquid chromatography. The analytical method was validated prior to the start of study. Cmax (Peak Plasma Concentration), Tmax (Time to achieve maximum Plasma Concentration), AUC0-72 (Area under plasma concentration time curve 0 to 72 hours), AUC0-∞ (Area under plasma concentration time curve 0 to ∞) and T½ (Elimination half-life) and Kel (Elimination rate constant) were calculated and 80-120% margin (90% confidence interval) was used to assess bioequivalence. ANOVA test was used to analyze the data at P-value of 0.05. All volunteers completed the study. The log-transformed values of Cmax, Tmax, AUC0-t, and AUC0-∞ of the both formulations were within the specified limits and were bioequivalent according to the regulatory definition of bioequivalence based on the rate and extent of absorption. Both products can be considered equally effective in medical practice. Keywords: Bioavailability, Bioequivalence, healthy volunteer, Nepal, phenytoin sodium.

scholarly journals A mixed diet supplemented with l-arabinose does not alter glycaemic or insulinaemic responses in healthy human subjects

2014 ◽  
Vol 113 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Kia Halschou-Jensen ◽  
Knud E. Bach Knudsen ◽  
Søren Nielsen ◽  
Klaus Bukhave ◽  
Jens R. Andersen
Keyword(s):  
Plasma Concentration ◽  
Wheat Flour ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Mixed Meal ◽  
Double Blind ◽  
C Peptide ◽  
Healthy Men ◽  
Positive Effects ◽  
Inhibiting Effect

In addition to a yet-to-be published study showing arabinose to have an inhibiting effect on maltase, in vitro studies have shown l-arabinose to exert an inhibiting effect on small-intestinal sucrase and maltase and the consumption of a sucrose-rich drink containing l-arabinose to exert positive effects on postprandial blood glucose, insulin and C-peptide responses in humans. However, the effects of adding l-arabinose to mixed meals on the indices of glucose control are unknown. The purpose of the present study was to investigate whether the positive effects of l-arabinose added to a sugar drink could be reproduced in subjects consuming a mixed meal containing sucrose and/or starch from wheat flour. A total of seventeen healthy men participated in study 1, a randomised, double-blind, cross-over trial. In this study, the subjects consumed two different breakfast meals containing sucrose and starch from wheat flour (meal A) or starch from wheat flour (meal B) supplemented with 0, 5 and 10 % l-arabinose by weight after a 12 h fast. A total of six healthy men participated in study 2, a randomised, double-blind, cross-over trial. In this study, the subjects also consumed meal B served in two different textures and a liquid meal with maltose supplemented with 0 and 20 % l-arabinose. In addition, 1·5 g of paracetamol was chosen as an indirect marker to assess gastric emptying. Postprandial plasma glucose, insulin and C-peptide concentrations were measured regularly for 3 h. The results of the present study showed that the peak plasma concentration, time to reach peak plasma concentration or AUC values of glucose, insulin and C-peptide were not altered after consumption of the test meals. Overall, it was not possible to reproduce the beneficial effects of l-arabinose added to sucrose drinks when l-arabinose was mixed in a solid or semi-solid mixed meal.

scholarly journals Enhanced Oral Bioavailability of Domperidone with Piperine in Male Wistar Rats: Involvement of CYP3A1 and P-gp Inhibition

2017 ◽  
Vol 20 ◽  
pp. 28 ◽  
Author(s):  
Bhargavi Latha Athukuri ◽  
Prasad Neerati
Keyword(s):  
Plasma Concentration ◽  
Oral Bioavailability ◽  
Wistar Rats ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Elimination Rate ◽  
Intestinal Transport ◽  
Control Group ◽  
Maximum Plasma ◽  
Male Wistar Rats

Purpose: Domperidone is a commonly used antiemetic drug. The oral bioavailability of domperidone is very low due to its rapid first pass metabolism in the intestine and liver. Piperine, the main alkaloid present in black pepper has been reported to show inhibitory effects on Cytochrome P-450 (CYP-450) enzymes and P-glycoprotein (P-gp). In the present study we investigated the effect of piperine pretreatment on the intestinal transport and oral bioavailability of domperidone in male Wistar rats. Methods: The intestinal transport of domperidone was evaluated by an in-vitro non-everted sac method and in-situ single pass intestinal perfusion (SPIP) study. The oral pharmacokinetics of domperidone was evaluated by conducting oral bioavailability study in rats. Results: A statistically significant improvement in apparent permeability (Papp) was observed in rats pretreated with piperine compared to the respective control group. The effective permeability (Peff) of domperidone was increased in the ileum of the piperine treated group. Following pretreatment with piperine, the peak plasma concentration (Cmax) and area under the concentration- time curve (AUC) were significantly increased. A significant decrease in time to reach maximum plasma concentration (Tmax), clearance and elimination rate constant (Kel) was observed in rats pretreated with piperine. Conclusions: Piperine enhanced the oral bioavailability of domperidone by inhibiting CYP3A1 and P-gp in rats. This observation suggests the possibility that the combination of piperine with other CYP3A4 and P-gp dual substrates may also improve bioavailability. Further clinical studies are recommended to verify this drug interaction in human volunteers and patients. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Efficacy of guar gum-based ronidazole capsules as a treatment for Tritrichomonas foetus infection in cats

2016 ◽  
Vol 19 (2) ◽  
pp. 177-184 ◽  
Author(s):  
Aurélien Grellet ◽  
Seyf Eddine Makhlouf ◽  
Loic Desquilbet ◽  
Fani Hovhannessian ◽  
Cassandre Boogaerts ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Placebo Group ◽  
Plasma Concentration ◽  
Guar Gum ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Maximum Plasma Concentration ◽  
Maximum Plasma ◽  
Tritrichomonas Foetus ◽  
Significant Difference

Objectives The aims of the study were to determine the in vitro drug release of guar gum-coated capsules of ronidazole, and to evaluate the pharmacokinetics and efficacy of this formulation for the treatment of cats naturally infected with Tritrichomonas foetus. Methods The pharmacokinetics of ronidazole were evaluated in five healthy cats and five cats infected with T foetus. In a second step, the clinical efficacy of these capsules was evaluated by a controlled, randomised, double-blind clinical trial performed in 47 infected cats from French catteries. In this study, cats were randomly allocated to either the ronidazole treatment group (n = 25) or a placebo group (n = 22). Ronidazole (30 mg/kg) q24h for 14 days was administered to the treated cats. After 14 days of treatment, the presence of T foetus was tested by conventional PCR assay. Results In the pharmacokinetic study, a delayed peak plasma concentration was observed in healthy and infected cats, with no significant difference between these two groups (mean geometric mean of 9 h for time to maximum plasma concentration [Tmax], 21.6 µg/ml for time to maximum plasma concentration [Cmax] and 467.4 μg/h/ml for the area under the curve [AUC] in healthy cats; and 9.4 h for Tmax, 17.1 µg/ml for Cmax and 481 μg/h/ml for AUC in infected cats). In the clinical trial, T foetus was detected in 16% of cats from the treated group and 82% of cats from the placebo group at the end of the study ( P <0.001). No clinical signs of adverse drug reactions were observed. Conclusions and relevance Oral administration of guar gum-coated capsules of ronidazole at a dose of 30 mg/kg once daily for 14 days delays the peak plasma concentration and eradicates infection in most cases.

Pharmacokinetics of solid lipid Boswellia serrata particles in healthy subjects

2021 ◽  
Vol 36 (3) ◽  
pp. 215-221
Author(s):  
Preeti D. Kulkarni ◽  
Neena D. Damle ◽  
Lal Hingorani ◽  
Vaidhun H. Bhaskar ◽  
Minal R. Ghante ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Oral Bioavailability ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Maximum Plasma ◽  
Boswellic Acid ◽  
Healthy Human ◽  
Boswellia Serrata ◽  
Solid Lipid ◽  
Human Volunteers

Abstract Objectives The anti-inflammatory activity of Boswellia serrata extracts (BSE) is well known. BSE comprises boswellic acids (BA) such as 3-O-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) as major constituents. One of the limitations of BAs is their poor oral bioavailability. The aim of the study was to prepare solid lipid particles of Boswellia serrata extract (SLBSP) to enhance the bioavailability of BAs. Methods The pharmacokinetic profile of BAs was studied in 10 healthy human volunteers following a single oral dose of 333 mg of SLBSP. Pharmacokinetic blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h post drug administration. Plasma KBA and AKBA levels were measured using a validated LC-MS/MS method. Pharmacokinetics parameters were estimated using Pheonix WinNonlin (Build 6.4.0.768) software. Results Ten healthy human volunteers were included and peak plasma concentration was achieved in 1.5 and 2.3 h for AKBA and KBA respectively. Maximum plasma concentration (C max) was 8.04 ± 1.67 ng/mL for AKBA and 23.83 ± 4.41 ng/mL for KBA whereas the corresponding area under the concentration-time curve (AUC) was 136.7 ± 56.77 ng/mL*h and 165.7 ± 24.5 ng/mL*h respectively. The elimination half-life (t 1/2) of AKBA and KBA was 6.8 ± 3.0 h and 2.45 ± 0.3 h respectively. Conclusions The SLBSP formulation of BSE showed enhanced oral bioavailability of BAs compared with historically reported data of unformulated BSE.

scholarly journals Effects of the Antifungals Voriconazole and Fluconazole on the Pharmacokinetics of S-(+)- and R-(−)-Ibuprofen

2006 ◽  
Vol 50 (6) ◽  
pp. 1967-1972 ◽  
Author(s):  
Ville-Veikko Hynninen ◽  
Klaus T. Olkkola ◽  
Kari Leino ◽  
Stefan Lundgren ◽  
Pertti J. Neuvonen ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Peak Plasma ◽  
Peak Plasma Concentration ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Time Curve ◽  
Respective Control ◽  
Control Value ◽  
Racemic Ibuprofen ◽  
The Mean

ABSTRACT Our objective was to study the effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of S-(+)- and R-(−)-ibuprofen. Twelve healthy male volunteers took a single oral dose of 400 mg racemic ibuprofen in a randomized order either alone, after ingestion of voriconazole at 400 mg twice daily on the first day and 200 mg twice daily on the second day, or after ingestion of fluconazole at 400 mg on the first day and 200 mg on the second day. Ibuprofen was ingested 1 h after administration of the last dose of voriconazole or fluconazole. Plasma concentrations of S-(+)- and R-(−)-ibuprofen were measured for up to 24 h. In the voriconazole phase, the mean area under the plasma concentration-time curve (AUC) of S-(+)-ibuprofen was 205% (P < 0.001) of the respective control value and the mean peak plasma concentration (C max) was 122% (P < 0.01) of the respective control value. The mean elimination half-life (t 1/2) was prolonged from 2.4 to 3.2 h (P < 0.01) by voriconazole. In the fluconazole phase, the mean AUC of S-(+)-ibuprofen was 183% of the control value (P < 0.001) and its mean C max was 116% of the control value (P < 0.05). The mean t 1/2 of S-(+)-ibuprofen was prolonged from 2.4 to 3.1 h (P < 0.05) by fluconazole. The geometric mean S-(+)-ibuprofen AUC ratios in the voriconazole and fluconazole phases were 2.01 (90% confidence interval [CI], 1.80 to 2.22) and 1.82 (90% CI, 1.72 to 1.91), respectively, i.e., above the bioequivalence acceptance upper limit of 1.25. Voriconazole and fluconazole had only weak effects on the pharmacokinetics of R-(−)-ibuprofen. In conclusion, voriconazole and fluconazole increased the levels of exposure to S-(+)-ibuprofen 2- and 1.8-fold, respectively. This was likely caused by inhibition of the cytochrome P450 2C9-mediated metabolism of S-(+)-ibuprofen. A reduction of the ibuprofen dosage should be considered when ibuprofen is coadministered with voriconazole or fluconazole, especially when the initial ibuprofen dose is high.

Absorption, conjugation and excretion of the flavanones, naringenin and hesperetin from α-rhamnosidase-treated orange juice in human subjects

2010 ◽  
Vol 103 (11) ◽  
pp. 1602-1609 ◽  
Author(s):  
Lea Bredsdorff ◽  
Inge Lise F. Nielsen ◽  
Salka E. Rasmussen ◽  
Claus Cornett ◽  
Denis Barron ◽  
...  
Keyword(s):  
Small Intestine ◽  
Plasma Concentration ◽  
Crossover Study ◽  
Orange Juice ◽  
Peak Plasma ◽  
Human Subjects ◽  
Peak Plasma Concentration ◽  
Double Blind ◽  
Time Curve ◽  
Time Points

We have determined the absorption, conjugation and excretion of naringenin-7-O-rutinoside (narirutin) compared to the corresponding glucoside in an orange juice matrix in human subjects. Healthy volunteers (eight men and eight women), in a double blind, randomised, crossover study, consumed orange juice with (1) natural content of naringenin-7-O-rutinoside; (2) α-rhamnosidase-treated to yield naringenin-7-O-glucoside. Blood was sampled at twelve time points and three fractions of urine were collected over 24 h. The area under the plasma–time curve of naringenin from (2) α-rhamnosidase-treated orange juice was increased about 4-fold (P < 0·0001), peak plasma concentration (Cmax) was 5·4-fold higher (P < 0·0001) and Tmax was decreased from 311 to 92 min (P = 0·002) compared to untreated orange juice (1), indicating a change in absorption site from the colon to the small intestine. Furthermore, the amount in urine was increased from 7 to 47 % (P < 0·0001) of the dose after consumption of the α-rhamnosidase-treated orange juice (2). All urine samples contained both naringenin-7- and -4′-O-glucuronides. In addition, to examine the effect of dose and α-rhamnosidase treatment on hesperetin conjugate profiles, a further treatment where (3) orange juice fortified with three times the original content of hesperetin-7-O-rutinoside was used. Five hesperetin metabolites (3′-O-glucuronide; 7-O-glucuronide; 5,7-O-diglucuronide; 3′,7-O-diglucuronide; 3′-O-sulphate) were present after all treatments (1–3), with the same profile of the conjugates. The present data show that bioavailability of naringenin is increased by conversion from rutinoside to glucoside, but the profile of the conjugates of flavanones formed and excreted in urine is neither affected by the absorption site nor by a 3-fold change in dose.

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