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Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : Seville orange juiceType of experiment : humanType of animal : -Type of study : Cross overN(Total) : 10* (M/F = 5/5)N(Treatment) : 10 (M/F = 5/5)Sex : Both sexAge : 21 - 32 yrs.Route : Oral administrationDose/Conc.(herb) : a single oral dose of a felodipine 10-mg extended-release tablet with 240 mL of Seville orange juiceDuration : Peripheral venous blood (7 mL) was collected just before felodipine and juice administration and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, and 24 hours thereafterType of interaction : PharmacokineticsInteraction with drug : FelodipineDose/Conc.(drug) : a single oral dose of felodipine 10-mg extended-release tabletResult : PositiveRemark : Result: The felodipine area under the plasma concentration-time curve was increased by 76% and 93% after Seville orange juice and grapefruit juice ingestion, respectively, compared with common orange juice. The effects of Seville orange juice and grapefruit juice were similar in that the felodipine maximum concentration was augmented while the terminal elimination half-life was unchanged and the dehydrofelodipine area under the plasma concentration time-curve was increased, but the dehydrofelodipine-felodipine area under the plasma concentration-time curve ratio was reduced. *Subject toal: Subjects were healthy nonsmoking volunteers.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : Dilute grapefruit juiceType of experiment : humanType of animal : -Type of study : Cross overN(Total) : 10* (M/F = 5/5)N(Treatment) : 10 (M/F = 5/5)Sex : Both sexAge : 21 - 32 yrs.Route : Oral administrationDose/Conc.(herb) : a single oral of a felodipine 10-mg extended-release tablet with 240 mL of dilute grapefruit juice (that contained equivalent total molar concentrations of bergamottin plus 6',7'-dihydroxybergamottin)Duration : Peripheral venous blood (7 mL) was collected just before felodipine and juice administration and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, and 24 hours thereafterType of interaction : PharmacokineticsInteraction with drug : FelodipineDose/Conc.(drug) : a single oral dose of felodipine 10-mg extended-release tabletResult : PositiveRemark : Result: The felodipine area under the plasma concentration-time curve was increased by 76% and 93% after Seville orange juice and grapefruit juice ingestion, respectively, compared with common orange juice. The effects of Seville orange juice and grapefruit juice were similar in that the felodipine maximum concentration was augmented while the terminal elimination half-life was unchanged and the dehydrofelodipine area under the plasma concentration time-curve was increased, but the dehydrofelodipine-felodipine area under the plasma concentration-time curve ratio was reduced. *Subject toal: Subjects were healthy nonsmoking volunteers.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : BergaptenType of experiment : in vitroType of animal : -Type of study : -N(Total) : -N(Treatment) : -Sex : -Age : -Route : -Dose/Conc.(herb) : For the reversible inhibition study, 22 microliters of cDNA-expressed human CYP3A4 (200 pmol/mL) was preincubated with 10 microliters of freshly prepared NADPH-generating system (yielding final concentrations of 1 mmol/L NADP+, 10 mmol/L of glucose-6-phosphate, and 1 U/mL of glucose-6-phosphate dehydrogenase) and 950 microliters of phosphate buffer (0.1 mol/L or potassium phosphate, 1 mmol/L of ethylenediaminetetraacetic acid, 5 mmol/L magnesium chloride, pH 7.4) at 37 degrees celsius. After 3 minutes, 10 microliters of 0.1, 1, or 10 mol/L bergapten was added, followed by 10 microliters of 0.5 mmol/L saquinavir.Duration : 15 minType of interaction : PharmacokineticsInteraction with drug : SaquinavirDose/Conc.(drug) : 10 microliter of 0.5 mmol/L saquinavirResult : PositiveRemark : Result: Preliminary kinetic studies showed that metabolism of saquinavir to its major metabolite, M-7, were reversibly inhibited by bergapten with a 50% inhibitory concentration that ranged from 10 to 100 micromol/L. Subsequently, bergapten was shown to produce time- and concentration-dependent inhibition of the enzyme.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : BergaptenType of experiment : in vitroType of animal : -Type of study : -N(Total) : -N(Treatment) : -Sex : -Age : -Route : -Dose/Conc.(herb) : For the mechanism-based inhibition study, 25 microliters of cDNA-expressed human CYP3A4 (2 mmol/mL) was preincubated with 1.2 microliters of NADPH-generating system and 93 microliters of phosphate buffer. After 3 minutes, 10 microliters of bergapten was added to achieve final concentrations of 0, 0.1, 1, 10, or 100 micromol/L. After 0, 15, and 30 minutes, 10 microliters of reaction mixture was removed and added to 990 microliters of a solution composed of 10 microliters of 0.5 mmol/L of saquinavir, 10 microliters of NADPH-generating system, and 970 microliters of phosphate buffer.Duration : 15 minType of interaction : PharmacokineticsInteraction with drug : SaquinavirDose/Conc.(drug) : 10 microliter of 0.5 mmol/L saquinavirResult : PositiveRemark : Result: Preliminary kinetic studies showed that metabolism of saquinavir to its major metabolite, M-7, were reversibly inhibited by bergapten with a 50% inhibitory concentration that ranged from 10 to 100 micromol/L. Subsequently, bergapten was shown to produce time- and concentration-dependent inhibition of the enzyme.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : 6',7'-dihydroxybergamottinType of experiment : in vitroType of animal : -Type of study : -N(Total) : -N(Treatment) : -Sex : -Age : -Route : -Dose/Conc.(herb) : Caco-2 cell cultures were first preincubated with micromol/L of 6',7'-dihydroxybergamottin for 30 minutes and then incubated simultaneously with 6',7'-dihydroxybergamottin and midazolam (3 micromol/L) for 4 hours.Duration : 30 min. and 4 hr.Type of interaction : PharmacokineticsInteraction with drug : Midazolam*/Versed/DormicumDose/Conc.(drug) : midazolam (CYP3A probe) 3 micromol/LResult : PositiveRemark : Result: 6',7'-Dihydroxybergamottin (10 micromol/L) inhibited midazolam 1'-hydroxylation by 93% compared with control. Comparatively, the CYP3A4 inhibitors troleandomycin (30 micromol/L) and ketoconazole (1 and 10 micromol/L) inhibited midazolam 1'-hydroxylation by 60% and at least 75%, respectively. Mean control activities for mechanismbased inhibitor- and ketoconazole-treated cultures were 95 and 107 pmol per hour per culture, respectively.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : BergaptenType of experiment : in vitroType of animal : -Type of study : -N(Total) : -N(Treatment) : -Sex : -Age : -Route : -Dose/Conc.(herb) : Caco-2 cell cultures were first preincubated with 10 micromol/L of betgapten for 30 minutes and then incubated simultaneously with bergapten and midazolam (3 micromol/L) for 4 hours.Duration : 30 min. and 4 hr.Type of interaction : PharmacokineticsInteraction with drug : Midazolam*/Versed/DormicumDose/Conc.(drug) : midazolam (CYP3A probe) 3 micromol/LResult : EquivocalRemark : Result: Bergapten (10 micromol/L) inhibited midazolam 1'-hydroxylation only 34% compared with control. Comparatively, the CYP3A4 inhibitors troleandomycin (30 micromol/L) and ketoconazole (1 and 10 micromol/L) inhibited midazolam 1'-hydroxylation by 60% and at least 75%, respectively. Mean control activities for mechanismbased inhibitor- and ketoconazole-treated cultures were 95 and 107 pmol per hour culture, respectively.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : grapefruit juiceType of experiment : humanType of animal : -Type of study : Cross overN(Total) : 5* (M/F = 2/3)N(Treatment) : 5 (M/F = 2/3)Sex : Both sexAge : 20 - 37 yrs.Route : Oral administrationDose/Conc.(herb) : After an overnight fast, each subject was given a 10-mg extended-release tablet of felodipine with 240 mL of grapefruit juice. To control for the ethanol content (5%) in the orange juice-containing serum, ethanol was added to the orange juice and grapefruit juice to yield a final concentration of 5%.Duration : Blood (5 mL) was collected immediately before administration of felodipine with the juice and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours thereafterType of interaction : PharmacokineticsInteraction with drug : FelodipineDose/Conc.(drug) : A single tablet of 10-mg extended-release tablet of felodipineResult : PositiveRemark : Result: For every subject except subject B (who appeared to have minimal response to either grapefruit juice or grapefruit juice serum), both the AUC(0-Clast) and Cmax of felodipine with grapefruit juice were increased by at least 2.2-fold relative to plain orange juice. *Subject total: Subjects were healthy volunteers.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : grapefruit juice serum (aqueous extract)Type of experiment : humanType of animal : -Type of study : Cross overN(Total) : 5* (M/F = 2/3)N(Treatment) : 5 (M/F = 2/3)Sex : Both sexAge : 20 - 37 yrs.Route : Oral administrationDose/Conc.(herb) : After an overnight fast, each subject was given a 10-mg extended-release tablet of felodipine with 240 mL of grapefruit juice. To control for the ethanol content (5%) in the orange juice-containing serum, ethanol was added to the orange juice and grapefruit juice to yield a final concentration of 5%.Duration : Blood (5 mL) was collected immediately before administration of felodipine with the juice and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, and 24 hours thereafterType of interaction : PharmacokineticsInteraction with drug : FelodipineDose/Conc.(drug) : A single tablet of 10-mg extended-release tablet of felodipineResult : PositiveRemark : Result: For every subject except subject B (who appeared to have minimal response to either grapefruit juice or grapefruit juice serum), both the AUC(0-Clast) and Cmax of felodipine with grapefruit juice were increased by at least 2.2-fold relative to plain orange juice. *Subject total: Subjects were healthy volunteers.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : grapefruit juice serum (aqueous extract)Type of experiment : in vitroType of animal : -Type of study : -N(Total) : -N(Treatment) : -Sex : -Age : -Route : -Dose/Conc.(herb) : For the reversible inhibition study, triplicate incubation mixtures containing cDNA-expressed CYP3A4 (0.25 pmol), BFC (25 pmol/L), bovine serum albumin (40 microg/mL), and magnesium chloride (3 mmol/L) were brought up to 445 microL with potassium phosphate buffer (0.1 mol/L, pH 7.4) and prewarmed for 5 minutes in a shaking water bath at 37 degrees celsius. Five microliters of a 100-fold concentrated solution of serum was added such that the final concentration of serum in the incubations was identical to that in the juice administered to the human subjects (240 mL of orange juice-containing grapefruit juice serum). The reaction was initiated by adding 50 microL of 10-mmol/L nicotinamide adenine dinucleotide phosphate, reduced (NADPH, 1-mmol/L final concentration).Duration : 15 minType of interaction : PharmacokineticsInteraction with drug : -Dose/Conc.(drug) : -Result : PositiveRemark : Result: cDNA expressed enzyme was coincubated with the CYP3A4 probe substrate BFC plus serum (at the identical concentration present in the juice administered to human subjects). Relative to control (vehicle), serum inhibited CYP3A4 catalytic activity by 85%+/-5%. The 95% Cl for the difference was 10%+/-7%.
Part Used : น้ำจากผลActivity : CYP3A4 INHIBITIONSolvent/Active Compound : 6',7'-dihydroxybergamottin (DHB)Type of experiment : in vitroType of animal : -Type of study : -N(Total) : -N(Treatment) : -Sex : -Age : -Route : -Dose/Conc.(herb) : For the reversible inhibition study, triplicate incubation mixtures containing cDNA-expressed CYP3A4 (0.25 pmol), BFC (25 pmol/L), bovine serum albumin (40 microg/mL), and magnesium chloride (3 mmol/L) were brought up to 445 microL with potassium phosphate buffer (0.1 mol/L, pH 7.4) and prewarmed for 5 minutes in a shaking water bath at 37 degrees celsius and DHB (38 micromol/L) was added. The reaction was initiated by adding 50 microL of 10-mmol/L nicotinamide adenine dinucleotide phosphate, reduced (NADPH, 1-mmol/L final concentration).Duration : 15 minType of interaction : PharmacokineticsInteraction with drug : -Dose/Conc.(drug) : -Result : PositiveRemark : Result: cDNA expressed enzyme was coincubated with the CYP3A4 probe substrate BFC plus purified DHB (at the concentration measured in serum). Relative to control (vehicle), serum inhibited CYP3A4 catalytic activity by 75%+/-4%. The 95% Cl for the difference was 10%+/-7%.
