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Grapefruit Juice (grapefruit + juice)

Distribution by Scientific Domains
Medical Sciences71%
Chemistry28%

Selected Abstracts

Grapefruit Juice Enhances the Exposure to Oral Oxycodone

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2010
Tuija H. Nieminen
The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration,time curve (AUC0,,) by 1.7-fold (p < 0.001), the peak plasma concentration by 1.5-fold (p < 0.001) and the half-life of oxycodone by 1.2-fold (p < 0.001) as compared to the water. The metabolite-to-parent AUC0,, ratios (AUCm/AUCp) of noroxycodone and noroxymorphone decreased by 44% (p < 0.001) and 45% (p < 0.001), respectively. Oxymorphone AUC0,, increased by 1.6-fold (p < 0.01) after grapefruit juice, but the AUCm/AUCp remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use. [source]

Grapefruit juice,drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007
Whocely Victor de Castro
Abstract To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P-gp substrate, across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, bergamottin, 6,,7,-dihydroxybergamottin, 6,,7,-epoxybergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6,,7,-epoxybergamottin, was the most potent inhibitor (IC50,=,0.7 µM), followed by 6,,7,-dihydroxybergamottin (IC50,=,34 µM) and bergamottin that did not show any inhibition at concentrations up to 10 µM. The flavonoid aglycone naringenin was around 10-fold more potent than its glycoside naringin with IC50 values of 236 and 2409 µM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P-gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2808,2817, 2007 [source]

Grapefruit Juice Enhances the Exposure to Oral Oxycodone

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2010
Tuija H. Nieminen
The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration,time curve (AUC0,,) by 1.7-fold (p < 0.001), the peak plasma concentration by 1.5-fold (p < 0.001) and the half-life of oxycodone by 1.2-fold (p < 0.001) as compared to the water. The metabolite-to-parent AUC0,, ratios (AUCm/AUCp) of noroxycodone and noroxymorphone decreased by 44% (p < 0.001) and 45% (p < 0.001), respectively. Oxymorphone AUC0,, increased by 1.6-fold (p < 0.01) after grapefruit juice, but the AUCm/AUCp remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use. [source]

Stereoselective pharmacokinetics of cisapride in healthy volunteers and the effect of repeated administration of grapefruit juice

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2001
Zeruesenay Desta
Aims, To determine whether the pharmacokinetics of cisapride and its interaction with grapefruit juice are stereoselective. Methods, The study was a randomized, two-phase cross over design with a washout period of 2 weeks. Ten healthy volunteers were pretreated with either water or 200 ml double strength grapefruit juice three times a day for 2 days. On the 3rd each subject ingested a single 10 mg dose of rac -cisapride tablet. Double strength grapefruit juice (200 ml) or water was administered during cisapride dosing and 0.5 and 1.5 h thereafter. Blood samples were collected before and for 32 h after cisapride administration. Plasma concentrations of cisapride enantiomers were measured by a chiral h.p.l.c. method. A standard 12-lead ECG was recorded before cisapride administration (baseline) and 2, 5, 8, and 12 h later. Results, This study showed that cisapride pharmacokinetics are stereoselective. In control (water treated) subjects, the mean Cmax (30 ± 13.6 ng ml,1; P = 0.0008) and AUC(0, ,) (201 ± 161 ng ml,1 h; P = 0.029) of (,)-cisapride were significantly higher than the Cmax (10.5 ± 3.4 ng ml,1) and AUC(0, ,) (70 ± 51.5 ng ml,1 h) of (+)-cisapride. There was no marked difference in elimination half-life between (,)-cisapride (4.7 ± 2.7 h) and (+)-cisapride (4.8 ± 3 h). Compared with the water treated group, grapefruit juice significantly increased the mean Cmax of (,)-cisapride from 30 ± 13.6,55.5 ± 18 ng ml,1 (95% CI on mean difference, ,33, ,17; P = 0.00005) and of (+)-cisapride from 10.5 ± 3.4 to 18.4 ± 6.2 ng ml,1 (95% CI on mean difference, ,11.8, ,3.9, P = 0.00015). The mean AUC(0, ,) of (,)-cisapride was increased from 201 ± 161 to 521.6 ± 303 ng ml,1 h (95% CI on mean difference, ,439, ,202; P = 0.0002) and that of (+)-cisapride from 70 ± 51.5 to 170 ± 91 ng ml,1 h (95% CI on mean difference, ,143, ,53; P = 0.0005). The tmax was also significantly increased for both enantiomers (from 1.35 to 2.8 h for (,)-cisapride and from 1.75 to 2.9 h for (+)-cisapride in the control and grapefruit juice group, respectively; P < 0.05). The t½ of (,)-cisapride was significantly increased by grapefruit juice, while this change did not reach significant level for (+)-cisapride. The proportion of pharmacokinetic changes brought about by grapefruit juice was similar for both enantiomers, suggesting non-stereoselective interaction. We found no significant difference in mean QTc intervals between the water and grapefruit juice treated groups. Conclusions, The pharmacokinetics of cisapride is stereoselective. Grapefruit juice elevates plasma concentrations of both (,)- and (+)-cisapride, probably through inhibition of CYP3A in the intestine. At present, there are no data on whether the enantiomers exhibit stereoselective pharmacodynamic actions. If they do, determination of plasma concentrations of the individual enantiomers as opposed to those of racemic cisapride may better predict the degree of drug interaction, cardiac safety and prokinetic efficacy of cisapride. [source]

Grapefruit juice inhibits 11,-hydroxysteroid dehydrogenase in vivo, in man

CLINICAL ENDOCRINOLOGY, Issue 1 2003
Mario Palermo
No abstract is available for this article. [source]

Reduction of cis - and trans -1,2-epithio- p -menth-8-ene: preparation of new fragrant terpenoid thiols

FLAVOUR AND FRAGRANCE JOURNAL, Issue 1 2003
Karine Candela
Abstract The synthesis of 2-mercapto- p -menth-8-ene (3) and 1-mercapto- p -menth-8-ene (4) are described, starting, respectively, from thioepoxydation of (+)- trans -limonene 1,2-epoxide (1a) and (+)- cis -limonene 1,2-epoxide (1b) via hydride reduction of episulphides 2a and 2b. Structural determination of these sulphur-containing terpenoids was achieved by one- and two-dimensional NMR spectroscopy. The odours of these two new monoterpene thiols were described, respectively, as reminescent of grapefruit juice and as being typically alliaceous. Copyright © 2002 John Wiley & Sons, Ltd. [source]

MULTIVARIATE ANALYSIS FOR CLASSIFICATION OF COMMERCIAL GRAPEFRUIT JUICE PRODUCTS BY VOLATILE CONSTITUTES

JOURNAL OF FOOD QUALITY, Issue 3 2000
JORGE A. PINO
ABSTRACT Isolation of volatile constituents from fresh and processed grapefruit juice by a simple technique afforded up to 20 components in each juice type. Many of these constituents are known to contribute to grapefruit juice flavor. Multivariate analysis utilizing the concentration data of twelve constituents allowed classification of the juice samples according to processing conditions. The classification corresponded to expected flavor quality. [source]

Grapefruit juice,drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2007
Whocely Victor de Castro
Abstract To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P-gp substrate, across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, bergamottin, 6,,7,-dihydroxybergamottin, 6,,7,-epoxybergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6,,7,-epoxybergamottin, was the most potent inhibitor (IC50,=,0.7 µM), followed by 6,,7,-dihydroxybergamottin (IC50,=,34 µM) and bergamottin that did not show any inhibition at concentrations up to 10 µM. The flavonoid aglycone naringenin was around 10-fold more potent than its glycoside naringin with IC50 values of 236 and 2409 µM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P-gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2808,2817, 2007 [source]

Grapefruit Juice Enhances the Exposure to Oral Oxycodone

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 4 2010
Tuija H. Nieminen
The objective of this study was to examine the effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of oral oxycodone in a randomized cross-over study with two phases at an interval of 4 weeks. Twelve healthy volunteers ingested 200 ml of grapefruit juice or water t.i.d. for 5 days. An oral dose of oxycodone hydrochloride 10 mg was administered on day 4. Oxycodone, noroxycodone, oxymorphone and noroxymorphone concentrations were analysed from the plasma samples for 48 hr and behavioural and analgesic effects were recorded for 12 hr. Grapefruit juice increased the mean area under the oxycodone concentration,time curve (AUC0,,) by 1.7-fold (p < 0.001), the peak plasma concentration by 1.5-fold (p < 0.001) and the half-life of oxycodone by 1.2-fold (p < 0.001) as compared to the water. The metabolite-to-parent AUC0,, ratios (AUCm/AUCp) of noroxycodone and noroxymorphone decreased by 44% (p < 0.001) and 45% (p < 0.001), respectively. Oxymorphone AUC0,, increased by 1.6-fold (p < 0.01) after grapefruit juice, but the AUCm/AUCp remained unchanged. Pharmacodynamic changes were modest and only self-reported performance significantly impaired after grapefruit juice. Analgesic effects were not influenced. Grapefruit juice inhibited the CYP3A4-mediated first-pass metabolism of oxycodone, decreased the formation of noroxycodone and noroxymorphone and increased that of oxymorphone. We conclude that dietary consumption of grapefruit products may increase the concentrations and effects of oxycodone in clinical use. [source]

Inhibitory effects of various beverages on human recombinant sulfotransferase isoforms SULT1A1 and SULT1A3

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2007
Haruka Nishimuta
Abstract Sulfotransferase (SULT) 1A1 and SULT1A3 play important roles in the presystemic inactivation of ,2 agonists in the liver and intestine, respectively. The study aimed to investigate the inhibitory effects of grapefruit juice, orange juice, green tea, black tea and oolong tea and their constituents on the activities of SULT1A1 and SULT1A3. The activities of both SULT1A1 and SULT1A3 were significantly inhibited by all the beverages investigated at a concentration of 10%. The beverage constituents were tested in concentration ranges considered to be physiologically relevant. The grapefruit constituent, quercetin, completely inhibited SULT1A1, while quercetin and naringin both partially inhibited SULT1A3. The orange constituents, tangeretin and nobiletin, also completely inhibited SULT1A1. The tea constituents, (,)-epicatechin gallate and (,)-epigallocatechin gallate, both almost completely inhibited SULT1A1 and SULT1A3. Moreover, the theaflavin and thearubigin fractions of black tea both completely inhibited SULT1A1 and strongly inhibited SULT1A3. The inhibitory action of green tea on SULT1A3 was competitive, while that of black tea and oolong tea was mixed competitive/non-competitive. Mechanism-based inhibition was not observed with any beverage. In conclusion, various beverages, especially teas, inhibit the function of SULT1A3, and therefore may have the potential to increase the bioavailability of orally administered substrates of SULT1A3, such as ,2 agonists. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Stereoselective pharmacokinetics of cisapride in healthy volunteers and the effect of repeated administration of grapefruit juice

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 4 2001
Zeruesenay Desta
Aims, To determine whether the pharmacokinetics of cisapride and its interaction with grapefruit juice are stereoselective. Methods, The study was a randomized, two-phase cross over design with a washout period of 2 weeks. Ten healthy volunteers were pretreated with either water or 200 ml double strength grapefruit juice three times a day for 2 days. On the 3rd each subject ingested a single 10 mg dose of rac -cisapride tablet. Double strength grapefruit juice (200 ml) or water was administered during cisapride dosing and 0.5 and 1.5 h thereafter. Blood samples were collected before and for 32 h after cisapride administration. Plasma concentrations of cisapride enantiomers were measured by a chiral h.p.l.c. method. A standard 12-lead ECG was recorded before cisapride administration (baseline) and 2, 5, 8, and 12 h later. Results, This study showed that cisapride pharmacokinetics are stereoselective. In control (water treated) subjects, the mean Cmax (30 ± 13.6 ng ml,1; P = 0.0008) and AUC(0, ,) (201 ± 161 ng ml,1 h; P = 0.029) of (,)-cisapride were significantly higher than the Cmax (10.5 ± 3.4 ng ml,1) and AUC(0, ,) (70 ± 51.5 ng ml,1 h) of (+)-cisapride. There was no marked difference in elimination half-life between (,)-cisapride (4.7 ± 2.7 h) and (+)-cisapride (4.8 ± 3 h). Compared with the water treated group, grapefruit juice significantly increased the mean Cmax of (,)-cisapride from 30 ± 13.6,55.5 ± 18 ng ml,1 (95% CI on mean difference, ,33, ,17; P = 0.00005) and of (+)-cisapride from 10.5 ± 3.4 to 18.4 ± 6.2 ng ml,1 (95% CI on mean difference, ,11.8, ,3.9, P = 0.00015). The mean AUC(0, ,) of (,)-cisapride was increased from 201 ± 161 to 521.6 ± 303 ng ml,1 h (95% CI on mean difference, ,439, ,202; P = 0.0002) and that of (+)-cisapride from 70 ± 51.5 to 170 ± 91 ng ml,1 h (95% CI on mean difference, ,143, ,53; P = 0.0005). The tmax was also significantly increased for both enantiomers (from 1.35 to 2.8 h for (,)-cisapride and from 1.75 to 2.9 h for (+)-cisapride in the control and grapefruit juice group, respectively; P < 0.05). The t½ of (,)-cisapride was significantly increased by grapefruit juice, while this change did not reach significant level for (+)-cisapride. The proportion of pharmacokinetic changes brought about by grapefruit juice was similar for both enantiomers, suggesting non-stereoselective interaction. We found no significant difference in mean QTc intervals between the water and grapefruit juice treated groups. Conclusions, The pharmacokinetics of cisapride is stereoselective. Grapefruit juice elevates plasma concentrations of both (,)- and (+)-cisapride, probably through inhibition of CYP3A in the intestine. At present, there are no data on whether the enantiomers exhibit stereoselective pharmacodynamic actions. If they do, determination of plasma concentrations of the individual enantiomers as opposed to those of racemic cisapride may better predict the degree of drug interaction, cardiac safety and prokinetic efficacy of cisapride. [source]