Grapefruit Juice Research Articles

Drug interaction between shoseiryuto extract or catechins and fexofenadine through organic-anion-transporting polypeptide 1A2 In vitro

Objective: Fexofenadine is an anti-allergy drug frequently used to treat rhinitis, which is absorbed through organic-anion-transporting polypeptide (OATP) 1A2 in the intestine. Clinical studies have revealed that grapefruit juice inhibits OATP1A2 to reduce the absorption of fexofenadine. In Japanese traditional Kampo medicine, shoseiryuto, a formula composed of eight crude drugs, is frequently used to treat allergic rhinitis, especially cases of pollinosis. The objective of this study is to present the drug information regarding the interaction between shoseiryuto and fexofenadine through OATP1A2. Materials and Methods: We established human embryonic kidney 293 cells stably expressing OATP1A2 and evaluated the inhibitory effects of the extracts of shoseiryuto and its herbal components on the uptake of fexofenadine into the cells. Results: Shoseiryuto extract inhibited fexofenadine uptake in a concentration-dependent manner with an IC50 value of 238 μg/ml. The inhibitory titer of shoseiryuto was much lower than that of grapefruit juice, and it is predicted that shoseiryuto could not pharmacokinetically interact interaction with fexofenadine through OATP1A2. Among the eight herbal components of shoseiryuto, the extracts of the terrestrial stem of Ephedra sinica and the root and stolon of Glycyrrhiza uralensis inhibited fexofenadine uptake with IC50 values of 102 and 89 μg/ml, respectively. We isolated catechin as the active ingredient from the extract of the terrestrial stem of E. sinica. Catechins inhibited the uptake of fexofenadine in a concentration-dependent manner, and the IC50 values of epicatechin (EC) gallate, epigallocatechin (EGC) gallate, EGC, catechin, and EC were 11, 26, 41, 52, and 96 μM, respectively. Conclusion: These results would contribute to the safe and effective use of shoseiryuto in clinics. Abbreviations used: CYP: Cytochrome P450; JPXVII: The 17th Edition of the Japanese Pharmacopoeia; EC: Epicatechin; ECG: Epicatechin gallate; EGC: Epigallocatechin; EGCG: Epigallocatechin gallate; HBSS: Hanks' balanced salt solution; HEK: Human embryonic kidney; OATP: Organic-anion-transporting polypeptide; PBS: Phosphate-buffered saline; PHB: p-hydroxybenzoic acid butyl ester.

Natural combination of phenolic glycosides from fruits resists pro-oxidant insults to colon cells and enhances intrinsic antioxidant status in mice.

A combination of fresh fruits adequately supplying required nutrients is likely to have better health benefits by virtue of the synergistic/additive effect of its natural constituents. With this view and aiming to obtain phenolic glycosides in combination, fresh apple, grape, orange, pomegranate, and sapota fruit juices were combined and lyophilized. An aqueous extract of this fruit combination (AEFC) had polyphenols as a major constituent (47.36 μg GAE/mL) and LC-MS analysis documented the presence of cyanidin and pallidol 3-O-glucosides, phloridzin, delphinidin-3-O-rutinoside, kaempferol-3-O-pentoside, quercetin-3-O-rutinoside, trans-caffeic acid. Corroborating this, AEFC exhibited significant DPPH and superoxide radical scavenging activities (IC50values 43.63 and 49.01 μg/mL) and protected colon epithelial cells (HCT-15) against H2O2 and AAPH induced cell death by 40 and 72.62% and buthionine sulfoximine (BSO) induced GSH depletion by 52.43%. In normal Swiss albino mice, administration of AEFC for over 30 days improved hepatic and renal GPx, SOD, and catalase activities and GSH levels. The study thus suggests the combinatorial effects of natural phenolic glycosides from fruits in resisting oxidative insults and associated disease pathology.

Development and validation of a volumetric absorptive microsampling assay for analysis of voriconazole and voriconazole N-oxide in human whole blood

Voriconazole is a broad-spectrum antifungal triazole drug for the treatment of invasive fungal infections. It is extensively metabolized by hepatic drug metabolizing enzymes cytochrome (CYP) 2C19 and CYP3A4. Selective inhibition of intestinal CYP3A4 by grapefruit juice may increase the oral bioavailability of voriconazole in children. To test this hypothesis it is necessary to develop a sensitive assay for measuring voriconazole and its major metabolites in a small volume of blood. Mitra® devices from Neoteryx were employed to develop and validate the assay for the quantitation of voriconazole and voriconazole N-oxide. Mitra® devices utilize volumetric absorptive microsampling (VAMS™) technology that enables accurate and precise collection of a fixed volume (10 μL of blood), reducing or eliminating the volumetric blood hematocrit assay-bias associated with the dried blood spotting technique. We developed an ultra-performance liquid chromatographic method with tandem mass spectrometry detection for quantification of voriconazole and voriconazole N-oxide. Sample extraction of Mitra® devices, followed by reversed-phase chromatographic separation and selective detection using tandem mass spectrometry with a 4.00 minute runtime per sample was employed. Standard curves were linear between 10.0 to 10,000 ng/mL for both voriconazole and voriconazole N-oxide. Intra- and inter-day accuracy were within 87–102% and precision (CV) was <12% based on a 3-day validation study. Recoveries were ≥94 % for voriconazole and ≥87 % for voriconazole N-oxide. Voriconazole and voriconazole N-oxide were stable in human whole blood under assay conditions (19 h at room temperature and 24 h in autosampler). Voriconazole was stable for 1-month in dried microsamples under different conditions (4, −20 and −78 °C). This assay provides an efficient quantitation of voriconazole and voriconazole N-oxide and is ready to be implemented for the analysis of whole blood microsamples in a pediatric clinical trial investigating the impact of intestinal inhibition of CYP3A4 on voriconazole pharmacokinetics.

NARINGIN REVEALS AMELIORATIVE PROPERTY OVER ELEVATED OXIDATIVE STRESS LEVELS IN ANIMAL MODELS

Oxidative stress (OxiS) has been implicated in the pathogenesis of many diseases. Free radicals interact with different cell components including DNA, proteins, and lipids to become stable. In this process, these free radicals damage the integrity of these biological moieties and result in various health implications. Naringin (NG), a naturally occurring phytochemical commonly found in grapefruit juice has been explored for its protective role against OxiS. In this short review paper, an attempt has been made to compile the study reports revealing the antioxidative nature of NG in different animal models. Studies have reported NG as a potential antioxidant in various health ailments including diabetes, cardiac fibrosis, cognitive dysfunction, and neurodegeneration.

New prospects for immersed hollow-fiber membranes in fruit juices microfiltration: Case of grapefruit juice

Side-stream tubular membranes are largely used to perform cross-flow microfiltration of fruit juices. However, this configuration presents well-known drawbacks (e.g. energy consumption). Immersed membranes configurations have been developed in many fields to overcome these disadvantages. This paper investigates for the first time the possibility of using immersed configuration for fruit juices microfiltration. Firstly, a lab-scale methodology was adopted to characterize the fouling propensity of the juice, while studying the impact of transmembrane pressure, membrane material and the role of large particles on the juice fouling behavior. Secondly, pilot-scale experiments were performed to identify the optimal operating conditions for both configurations. Both lab-scale and pilot-scale experiments suggested that the operating conditions of immersed configuration (no removal of large particles, low pressure and organic membranes) could be suitable to perform juice microfiltration. The optimal permeate flux of immersed configuration was in accordance with the ones reported in other fields. A productivity similar to the one related to side-stream configuration might be obtained through an increase of the filtration surface, made possible by the great packing density and low membrane cost related to immersed configuration. These findings offer new application for immersed membrane configuration in the microfiltration of delicate fruit juices.

Quality changes in high hydrostatic pressure and thermal pasteurized grapefruit juice during cold storage.

This study evaluated the effects of high hydrostatic pressure (HHP) and thermal pasteurization (TP) on microbial counts, physicochemical properties, antioxidant characteristics, naringin and naringenin contents, and naringinase activity of grapefruit juice during 21 days cold storage period. Results showed that HHP and TP significantly decreased the total microbial, coliform, and yeast counts. No significant differences between HHP-treated grapefruit juice (600MPa/5min) and untreated fruit juice with respect to physicochemical properties such as total titratable acidity, pH, and total soluble solids was observed after 21 days of storage. Although HHP affected the colour and antioxidant characteristics of grapefruit juice, the extent of effect was significantly lower than that for TP-treated fruit juice. This demonstrated that HHP could better maintain the original flavour and quality of grapefruit juice compared to TP. In addition, 92% naringinase activity was maintained in HHP-600 group on Day 21, which increased the degradation of bitter naringin into non-bitter naringenin during the cold storage of grapefruit juice. In summary, HHP can simultaneously maintain the microbiological safety of grapefruit juice along with its original quality characteristics. HHP can effectively extend the storage period and safety during cold chain transport, and hence highly applicable in the grapefruit juice industry.

The Yin-Yang of CYP3A4: a Bayesian meta-analysis to quantify inhibition and induction of CYP3A4 metabolism in humans and refine uncertainty factors for mixture risk assessment.

Quantifying differences in pharmacokinetics (PK) and toxicokinetics (TK) provides a science-based approach to refine uncertainty factors (UFs) for chemical risk assessment. Cytochrome P450 (CYP) 3A4-the major hepatic and intestinal human CYP-and the P-glycoprotein (Pgp) transporter share a vast range of common substrates for which PK may be modulated through inhibition or induction in the presence of grapefruit juice (GFJ) or St. John's wort (SJW), respectively. Here, an extensive literature search was performed on PK interactions for CYP3A4 and Pgp substrates after oral co-exposure to GFJ and SJW. Relevant data from 109 publications, extracted for both markers of acute (Cmax) and chronic [clearance and area under the plasma concentration-time curve (AUC)] exposure, were computed into a Bayesian hierarchical meta-analysis model. Bioavailability (F) and substrate fraction metabolised by CYP3A4 (Fm) were identified as the variables exhibiting the highest impact on the magnitude of interaction. The Bayesian meta-regression model developed provided good predictions for magnitudes of inhibition (maximum 5.3-fold with GFJ) and induction (maximum 2.3-fold with SJW). Integration of CYP3A4 variability, F, Fm and magnitude of interaction provided the basis to derive a range of CYP3A4 and Pgp-related UFs. Such CYP3A4 and Pgp-related UFs can be derived in the absence of human data using in vitro TK evidence for CYP3A4/Pgp inhibition or induction as conservative in silico options. The future development of quantitative in vitro-in vivo extrapolation models for mixture risk assessment is discussed with particular attention to integrating human in vitro and in vivo P/TK data on interactions with pathway-related variability.

Preparation of a Defined Gluten Hydrolysate for Diagnosis and Clinical Investigations of Wheat Hypersensitivities.

Gluten is the trigger for celiac disease (CD), non-celiac gluten/wheat sensitivity (NCGS), and wheat allergy. An oral food challenge is often needed for diagnosis, but there are no standardized gluten challenge materials with known composition available. To fill this gap, two materials, commercially available gluten and a food-grade gluten hydrolysate (pepgluten), were extensively characterized. Pepgluten was prepared from gluten by incubation with a pepsin dietary supplement and acetic acid at 37 °C for 120 min. The components of pepgluten were crude protein (707 mg/g), starch (104 mg/g), water (59 mg/g), fat (47 mg/g), dietary fiber (41 mg/g) and ash (11 mg/g). The protein/peptide fraction of pepgluten (1 g) contained equivalents derived from 369 mg gliadins and 196 mg glutenins, resulting in 565 mg total gluten equivalents, 25 mg albumins/globulins, 22 mg α-amylase/trypsin inhibitors and 48 mg pepsin capsule proteins. The slightly acidic, dough-like smell and bitter taste of pepgluten could be completely camouflaged in multivitamin juice with bitter lemon, grapefruit juice, or vegetable and fruit smoothies. Thus, pepgluten met the criteria for placebo-controlled challenges (active and placebo materials are identical regarding appearance, taste, smell, and texture) and is appropriate as a standard preparation for the oral food challenge and clinical investigations to study wheat hypersensitivities.

Grapefruit juice nutritional profile

Based on the published data on the content of nutritive (NS) and biologically active substances (BAS) and the results of studies of various samples of domestic industrial grapefruit juice, the article presents the nutrient profile of grapefruit juice containing data about more than 30 NS and BAS. Grapefruit juice is one of the relatively low-calorie fruit juices - 100 ml of grapefruit juice contains an average of 39 kcal. Like other citrus juices, it is rich in organic acids, the main of which is citric acid (0.8-2 g/100 ml). Potassium, magnesium, vitamin C, as well as flavonoids (mostly narigin) are the most significant for the estimation of nutritional and biological value of grapefruit juice of industrial production. A glass of grapefruit juice contains, on average, about 10% of the daily requirement in potassium, 6% - in magnesium and about 100% - in vitamin C. The amount of flavonoids in a glass of grapefruit juice provides up to 60% of the adequate daily intake. Conducted studies of fresh grapefruits purchased in the trade network show that the content of potassium, magnesium and vitamin C in grapefruit juice of industrial production is comparable to the content of these micronutrients in fresh fruits.

The effect of food and liquid pH on the integrity of enteric-coated beads from cysteamine bitartrate delayed-release capsules.

BackgroundCysteamine bitartrate delayed-release (DR) capsule (Procysbi®) is approved for treatment of nephropathic cystinosis in the USA, Canada, and the EU. The capsules contain cysteamine bitartrate beads that are enteric coated with acid-resistant Eudragit L 30 D-55, preventing drug release in the acidic stomach environment while allowing dissolution of the beads in the more alkaline environment of the small intestine. Patients who have difficulty swallowing capsules can open capsules, sprinkle beads onto 4 ounces of a suitable food or liquid, gently mix, and consume the entire content within 30 minutes. Foods found to be suitable for administration, and described in the Procysbi US labeling, include fruit juices (except grapefruit juice), applesauce, and berry jelly; there are minor variations in the foods and liquids recommended by regulatory authorities in other countries. This study aimed to assess the stability of enteric-coated beads exposed to additional foods at different conditions to expand the list of suitable foods for drug administration.MethodsFor each test condition, beads from eight opened 75 mg cysteamine bitartrate DR capsules were gently mixed with test food and maintained at a prespecified temperature and duration; remaining undissolved beads were then recovered from the food. The recovered beads were split into two portions: one assayed for remaining drug content and the other subjected to dissolution testing to assess the effect on the drug-release profile.ResultsThe results show that bead integrity was maintained when mixed with foods at pH values <5.5 at all time points when refrigerated (2°C–8°C) and at room (20°C–22°C) and lukewarm (37°C–41°C) temperatures. Bead integrity was not maintained when mixed with foods at pH values of ≥5.5 at room temperature.ConclusionThe results from this in vitro dissolution study help in identifying additional foods that may be used for the administration of cysteamine bitartrate DR beads from opened capsules using the sprinkle method.

Synthesis and Characterization of Bacterial Cellulose from Citrus-Based Sustainable Resources.

Citrus juices from whole oranges and grapefruits (discarded from open market) and aqueous extracts from citrus processing waste (mainly peels) were used for bacterial cellulose production by Komagataeibacter sucrofermentans DSM 15973. Grapefruit and orange juices yielded higher bacterial cellulose concentration (6.7 and 6.1 g/L, respectively) than lemon, grapefruit, and orange peels aqueous extracts (5.2, 5.0, and 2.9 g/L, respectively). Compared to the cellulosic fraction isolated from depectinated orange peel, bacterial cellulose produced from orange peel aqueous extract presented improved water-holding capacity (26.5 g water/g, 3-fold higher), degree of polymerization (up to 6-fold higher), and crystallinity index (35–86% depending on the method used). The presence of absorption bands at 3240 and 3270 cm–1 in the IR spectrum of bacterial cellulose indicated that the bacterial strain K. sucrofermentans synthesizes both Iα and Iβ cellulose types, whereas the signals in the 13C NMR spectrum demonstrated that Iα cellulose is the dominant type.

Sensory characterization of juice obtained via rehydration of freeze-dried and spray-dried grapefruit.

The acceptability of grapefruit juice obtained from rehydrated freeze-dried and spray-dried fruit was studied and compared with that of natural freshly squeezed juice and that of a commercial juice. The rheological properties, colour and solute concentration were determined. A sensory evaluation was developed to evaluate juice acceptability. Furthermore, a penalty analysis was used to determine the attributes with improvement potential as well as some CATA (check all that apply) questions, where consumers marked the most characteristic attributes of each sample. The rehydrated samples were different from the commercial and natural juices. When grapefruit is freeze-dried or spray-dried, gum arabic and bamboo fibre are added and part of the fruit pulp is present; this is not so in the other juices under study. This supposes greater viscosity, luminosity and chroma together with a reddish tone of the rehydrated juices, especially the freeze-dried ones. It also affects their acidity, astringency and sweetness. Rehydrating the freeze-dried or spray-dried powder to the level of the natural juice, instead of that of the crushed or liquidized grapefruit, and incorporating sugar at this stage would probably improve the quality of the samples. © 2018 Society of Chemical Industry.

Use of microbial models to evaluate the effect of UV-C light and trans-cinnamaldehyde on the native microbial load of grapefruit (Citrus × paradisi) juice

The aim of this research was to evaluate the storage stability (5 °C), and microbial modeling, of Rubi red grapefruit (Citrus × paradisi) juice treated with ultraviolet-C (UV-C) light (0, 10 and 20 min), alone or in combination with trans-cinnamaldehyde (trans-CAH) (0, 25 and 50 μg/mL). A 32 factorial design was used and data modeled with the Weibull, Modified Gompertz and Logistic models. A response surface model was used to evaluate the effect of modeling parameters for suggesting the optimum treatment conditions. Treated and some untreated juice lasted up to 9 days without physicochemical and microbial changes. At the higher combination of UV-C light and trans-CAH, the microbial load of grapefruit juice was maintained below 100 CFU/mL up to 15 days. For mesophiles, the three predictive models indicated that the parameters n and Nmax decreased and the parameters λ and tc increased as the combination of UV-C light and trans-CAH increased. The response surface modeling of the parameters obtained by the predictive models showed acceptable correlation for mesophiles (R2 = 0.815–0.977) but not for yeasts (R2 = 0.618–0.815). The three predictive models showed that, the concentration of trans-CAH had more effect on stopping the microbial growth than the UV-C light treatment.

Time-intensity and reaction-time methodology applied to the dynamic perception and liking of bitterness in relation to body mass index

There are very few studies which have considered perception temporality when relating perceived intensity and hedonic responses in relation to body mass index (BMI; kg/cm2). The aim of the present study was to determine the relationship between BMI with the dynamic perception and liking of bitter tasting solutions. For this purpose, two different categories of bitter products were applied: 6-n-propilthiouracil (PROP) solutions (0.010, 0.032 and 0.060 mmol/L) and commercial beverages (coffee, yerba mate infusion and grapefruit juice). The proposed methodology to evaluate perception and hedonic response was based on the measurement of reaction-time (R-T) and multiple-sip time-intensity (T-I) registers in people with a high BMI (25 < BMI < 30; overweight group) and a normal BMI (<25; normal-weight control group). The multiple-sip evaluation to describe perception of PROP solutions and liking of beverages was used as a more ecologically valid laboratory methodology to simulate a situation of usual consumption. In this sense, working with a multiple-sip design helped confirm that bitter taste has a cumulative effect since in every case the sip effect was significant when evaluating the maximum intensity; this effect was more important as the bitterness increased. Regarding the body weight group comparisons, the normal BMI group perceived bitter taste more intensely and the time to react to it was shorter (faster reaction) for both PROP solutions and the three beverages. Interestingly, even though the high BMI group rated the bitter taste as less intense, they had a lower level of acceptance than normal BMI. This result suggests that the hedonic rather than the sensory component might be playing a crucial role in the perception of bitter taste in individuals with high BMI.

Management of Idiopathic Nephrotic Syndrome: Co-Administration of Cyclosporine and Lyophilized Grapefruit Juice

Management of Idiopathic Nephrotic Syndrome: Co-Administration of Cyclosporine and Lyophilized Grapefruit Juice

Potentiating and synergistic effect of grapefruit juice on the antioxidant and anti-inflammatory activity of aripiprazole against hydrogen peroxide induced oxidative stress in mice

BackgroundDependence on antipsycotic drugs like aripriprazole (ARI) is increasing at alarming rate, hence, this study was undertaken to support the hypothesis that supplementation of Citrus paradisi(Grapefruit) juice having high concentration of polyphenols might potentiate and synergize the therapeutic effect of ARI, by increasing its bioavailability and inherent antioxidant potential. These benefits together might decrease the daily dosage of the ARI and thus alleviate the possible side effects of drug.MethodsIn this study the antioxidant and anti-inflammatory potential of ARI alone and in combination with GFJ was evaluated for hydrogen peroxide (H2O2) induced oxidative stress in mice. Seventy mice (4 weeks old), were randomly divided into seven groups. Group I: Control; Group II: H2O2 treated; Group III; ARI treated; Group IV GFJ treated; Group V: GFJ and H2O2 treated; Group VI; ARI and H2O2 treated; Group VII; ARI, GFJ and H2O2 treated. Serum levels of alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine kinase (CK), creatinine and total protein were measured. Furthermore, pro-inflammatory cytokines Interleukin (IL)-1α, IL-2, IL-10 and tumor necrosis factor-α (TNF-α) concentrations were also measured.ResultsThe mice group that was treated with ARI, GFJ or combination of the two showed significant improvement in the H2O2 altered parameters with the combination group showing more significant improvement than the ARI and GFJ alone groups indicating a synergistic and potentiating effect of the antioxidant and anti-inflammatory potential of GFJ on ARI.ConclusionSupplementing GFJ to ARI might increase an anti-oxidative potential of ARI due to inherent antioxidant and anti-inflammatory activity of GFJ and thus could alleviate the possible dosage dependent side effects of ARI.

Abstract 051: Genome-wide Association Study Identifies 12 Loci for Habitual Consumption of Bitter and Sweet Beverages

Introduction: Widely consumed beverages (e.g., soft drinks, coffee, tea) are critical sources of energy, added sugar and phytochemicals and are associated with obesity and chronic disease. Taste perception and preferences are highly heritable and strong determinants of food and beverage choice. We aimed to identify novel loci underlying habitual bitter and sweet beverage intake. Methods: We performed a genome-wide association study (GWAS) of self-reported bitter and sweet beverage intake in participants of European ancestry in the UK Biobank. Diet was assessed via multiple 24-h diet recalls (n=84703, subset) or questionnaire (n=335909, all). Bitter beverage intake was the sum of coffee, tea and grapefruit juice. Sweet beverage intake was the sum of artificially and sugar sweetened beverages and other fruit juice. Multivariable linear regression under an additive genetic model was applied. GW-significant (P &lt; 5х10 -8 ) SNPs were followed-up for replication in independent studies of European ancestry. Results: Multiple SNPs spanning 11 loci were associated with bitter beverage intake (P &lt;5х10 -8 , Table 1), and at least 5 of them reflected the caffeine content of coffee and tea. Multiple SNPs in the obesity candidate gene FTO were associated with sweet beverage intake (P &lt;5х10 -8 ). The effect size per allele ranged from 0.02 to 0.2 cup per day. Loci in/near AHR, CYP1A2, and FTO were associated with both bitter and sweet beverage intake but in opposite directions. Replication efforts are ongoing. So far, associations at all loci, except 1q25.2 and 2q36.2, were replicated (P range: 0.04 to 1.8x10 -8 ) in independent studies (n=17322) which provided 80% power for replicating 8 of these 12 loci at P=0.05. Conclusions: Loci linked to caffeine metabolism and obesity predisposition rather than taste are major determinants of beverage intake. These and other identified loci have been linked to chronic disease and risk factors, suggesting causal or pleiotropic effects. Our findings have potential public health and methodological implications.

Evaluation of Grapefruit Juice (Citrus paradisi) as an Alternative Disinfectant for Hatching Eggs

Evaluation of Grapefruit Juice (Citrus paradisi) as an Alternative Disinfectant for Hatching Eggs

Isomerization of feruloylputrescine in orange juice by light exposure.

Exposure to light may adversely affect the quality of foods. This investigation of how light exposure affects citrus (orange and mandarin blend) juice in polyethylene terephthalate (PET) bottles demonstrated that the isomeric form of a compound in the juice changed during storage. This compound was identified as feruloylputrescine (FP; CAS: 501-13-3; C14H20N2O3) using LC/MS (Q-TOF). LC/MS and NMR measurements showed that the content of the original form, trans-FP, decreased as it isomerized to cis-FP during storage. This phenomenon could be observed in citrus fruit juices containing FP, such orange and grapefruit juices. Therefore, determining the content of these two isomers of FP could be used to indicate the level of light exposure experienced by citrus fruit products.

Inhibitory Effect of Japanese Traditional Kampo Formula Frequently Prescribed in Gynecological Clinics on CYP3A4.

Recently, the use of herbal medicines has become popular, and information on drug interactions between herbal medicines and chemical drugs is needed in clinics. In Japan, the number of patients taking Japanese traditional Kampo medicines has been increasing, and the proper drug information about herb-drug interaction is highly demanded. The most established herb-drug interaction is the case of grapefruit juice (GFJ) via the inhibition on CYP3A4 expressed in the small intestine. In the present study, we compared the inhibitory titer on CYP3A4 between the target Kampo products and GFJ used as positive control. We evaluated the inhibitory effects of GFJ and three extracts of Kampo formulas frequently used in gynecological clinics on CYP3A4 in vitro and calculated the related titer of one-time dosage of Kampo formulas to GFJ in order to predict its effect on clinics. Although the extracts of these three Kampo formulas and the most of crude drug components in the formulas exhibited the inhibitory effects on CYP3A4 in some levels, the possibilities of tokishakuyakusan and keishibukuryogan to cause drug interaction can be quite low; however, it is possible that the excessive dosage of kamishoyosan may cause drug interaction with the substrate of CYP3A4 in clinics.