RESUMEN

A naringinase complex was chemically aminated prior to its immobilization on glyoxyl-agarose to develop a robust biocatalyst for juice debittering. The effects of amination on the optimal pH and temperature, thermal stability, and debittering performance were analyzed. Concentration of amino groups on catalysts surface increased in 36 %. Amination reduced the ß-glucosidase activity of naringinase complex; however, did not affect optimal pH and temperature of the enzyme and it favored immobilization, obtaining α-l-rhamnosidase and ß-d-glucosidase activities of 1.7 and 4.2 times the values obtained when the unmodified enzymes were immobilized. Amination favored the stability of the immobilized biocatalyst, retaining 100 % of both activities after 190 h at 30 °C and pH 3, while its non-aminated counterpart retained 80 and 52 % of α-rhamnosidase and ß-glucosidase activities, respectively. The immobilized catalyst showed a better performance in grapefruit juice debittering, obtaining a naringin conversion of 7 times the value obtained with the non-aminated catalyst.

Asunto(s)

RESUMEN

INTRODUCTION: There is a large body of preclinical data implicating that grapefruit juice (GJ) inhibits many CYP 450 isoforms. The potential of GJ-to-drug is of high relevance to clinical psychiatry, because a wide range of psychotropic medicines undergo CYP 450 metabolism and P-gp transport. AREAS COVERED: Relevant data were identified by searching the electronic databases up to February 2024. This work constitutes a summary of preclinical and clinical data on GJ impact on CYP 450 metabolism, P-glycoprotein, and organic anion-transporting polypeptides (OATPs), with focus on studies that assessed GJ-to-psychotropic drug interactions. Additionally, an unpublished case series of nine patients is provided. EXPERT OPINION: The impact of GJ on CYP 3A4 appears to be the critical mechanism for the majority of GJ-to-psychopharmacotherapy interactions described in human studies or case reports. However, there are studies and cases of patients clearly showing that this is not the only route explaining the GJ effect, and at times, this particular is of no relevance and that other CYP 450 isoforms as well as drug transporting proteins might be involved. The risk of GJ-to-psychotropic drugs needs to be further evaluated in a 'real-world' setting and apply not only measures of pharmacokinetics but also treatment effectiveness and safety.

Asunto(s)

RESUMEN

Aim: An eco-friendly ultra-performance liquid chromatography-tandem mass spectrometry method was developed to study the pharmacokinetics of rivaroxaban and ticagrelor in rat plasma, utilizing moxifloxacin as an internal standard. The food-drug interaction between grapefruit juice and these drugs was also investigated. Methods: Liquid-liquid extraction was used. A nonporous stationary phase Agilent® Poroshell 120EC C18 column was used with methanol: 0.1% aqueous formic acid (95:5 v/v) as a mobile phase. The detection was performed in multiple reaction monitoring mode using positive electrospray ionization. The method's validation was conducted in accordance with US FDA and European Medicines Agency guidelines. Results & conclusion: Grapefruit juice should be ingested with caution in patients treated with antithrombotic medications as it may increase their plasma concentration, inducing bleeding, and requires close clinical monitoring.

Asunto(s)

RESUMEN

Osteoarthritis (OA) is a common disorder that can affect any joint in the human body. This study aimed to examine the anti-arthritic properties of high and low doses of grapefruit juice (GFJ), as grapefruit appears to contain anti-inflammatory biochemicals. Forty male Sprague-Dawley rats weighing 170-180 g were divided into five groups. These groups comprised the untreated control group and osteoarthritic (Osteo) rats administered intra-articular injections of Freund's complete adjuvant (CFA; 0.5 mL; 1 mg/mL) as follows: OA rats administered low doses of GFJ (Osteo+GFJ (low); 5 mL/kg body weight (BW)); OA rats administered high doses of GFJ (Osteo+GFJ (high); 27 mL/kg BW); and OA rats administered diclofenac sodium (Osteo+Diclo) as a reference drug. Injections of CFA induced OA, as indicated by a significant increase in the serum levels of the inflammatory biomarkers C-reactive protein (CRP), interleukin-1ß (IL-1ß), and (prostaglandin (PGE2), as well as matrix metalloproteinases (MMP-1) and cathepsin K. The synovial levels of glycosaminoglycans (GAGs), tumor necrosis factor (TNF-α), and interleukin 6 (IL-6) also increased, with a concomitant reduction in osteocalcin levels. The administration of either high or low doses of GFJ reduced CRP, IL-1ß, PGE2, MMP-1, cathepsin K, and osteocalcin while increasing the synovial levels of GAGs, TNF-α, and IL-6, slowing cartilage degradation and boosting joint function. The results showed comparable histopathological and biochemical responses. A comparison of the treatments showed that high-dose GFJ had a greater chondroprotective effect than low-dose GFJ.

Asunto(s)

RESUMEN

Grapefruit has attracted much attention as a functional fruit, of which "Cocktail" is a special variety with low acidity. The present study aimed to investigate the effects of alcoholic fermentation on the non-volatile and volatile compounds of "Cocktail" grapefruit juice. To analyze, a non-targeted metabolomics method based on UPLC-MS/MS and volatiles analysis using GC-IMS were performed. A total of 1015 phytochemicals were identified, including 296 flavonoids and 145 phenolic acids, with noticeably increasing varieties and abundance following the fermentation. Also 57 volatile compounds were detected, and alcoholic fermentation was effective in modulating aromatic profiles of grapefruit juice, with terpenes and ketones decreasing, and alcohols increasing together with esters. Citraconic acid and ethyl butanoate were the most variable non-volatile and volatile substances, respectively. The results provide a wealth of information for the study of "Cocktail" grapefruit and will serve as a valuable reference for the large-scale production of grapefruit fermented juice in the future.

RESUMEN

Recent in vitro studies showed that grapefruit (Citrus × paradisi) flavonoid naringenin alters the function of cardiac ion channels. Here, we explored the effect of naringenin on cardiomyocyte action potentials (APs) using a detailed in silico model of ventricular electrophysiology. Concentration-dependent effects of naringenin on seven major cardiac ion channels were incorporated into the Tomek-Rodriguez modification of O'Hara-Rudy (ToR-ORd) human ventricular endocardium model. To investigate the sex-dependent effect of naringenin, previously reported sex-specific ionic modifications were implemented into the model. Next, populations of 1000 models accommodating intercellular variability were generated. The results show, naringenin at various concentrations prolonged AP duration (APD) in male and female cardiomyocytes. Pacing cells at higher frequencies abbreviated APD differently in males versus females; for example, at 3 Hz, 50 µM naringenin induced AP and calcium alternans only in the female cardiomyocyte. Finally, a population modeling approach corroborated that naringenin significantly prolonged APD in a concentration-dependent manner, with a larger effect in females than in males. In conclusion, our study demonstrates that the APD-prolonging effect of naringenin was larger in females, and that pacing at faster rates induces AP alternation earlier in females, suggesting a potentially higher proarrhythmic risk of naringenin in females than in males.

RESUMEN

A sensitive and selective UPLC-MS/MS method was developed for the synchronized determination of four drugs used in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), namely, azithromycin, apixaban, dexamethasone, and favipiravir in rat plasma. using a Poroshell 120 EC-C18 column (50 mm × 4.6 mm, 2.7 m) with a high-resolution ESI tandem mass spectrometer detection with multiple reaction monitoring. We used an Agilent Poroshell column, which is characterized by a stationary phase based on non-porous core particles. With a remarkable improvement in the number of theoretical plates and low column backpressure. In addition, the developed method was employed in studying the potential food-drug interaction of grapefruit juice (GFJ) with the selected drugs which affects their pharmacokinetics in rats. The LC-MS/MS operated in positive and negative ionization mode using two internal standards: moxifloxacin and chlorthalidone, respectively. Liquid- liquid extraction of the cited drugs from rat plasma was accomplished using diethyl ether: dichloromethane (70:30, v/v). The analytes were separated using methanol: 0.1 % formic acid in water (95: 5, v/v) as a mobile phase in isocratic mode of elution pumped at a flow rate of 0.3 mL/min. A detailed validation of the bio-analytical method was performed in accordance with US-FDA and EMA guidelines. Concerning the in vivo pharmacokinetic study, the statistical significance between the results of the test groups receiving GFJ along with the cited drugs and the control group was assessed demonstrating that GFJ increased the plasma concentration of azithromycin, apixaban, and dexamethasone. Accordingly, this food-drug interaction requires cautious ingestion of GFJ in patients using (SARS-CoV-2) medications as it can produce negative effects in the safety of the drug therapy. A potential drug-drug interaction is also suggested between those medications requiring a suitable dose adjustment.

RESUMEN

Naringin and limonin are the two main bitter compounds of citrus products such as grapefruit juice. The aim of this investigation was to evaluate the reduction in both bitter components simultaneously using a combined biochemical and physical approach. The proposed strategy was based on the use of heterofunctional supports with glyoxyl groups that allow for the covalent immobilization of naringinase, which hydrolyses naringin and alkyl groups that allow for the adsorption of limonin. The supports were butyl-glyoxyl agarose (BGA) and octyl-glyoxyl agarose (OGA), which were characterized in terms of aldehyde group quantification and FTIR analysis. The optimal pH and temperature of free and immobilized enzymes were assessed. The maximum enzyme loading capacity of supports was analyzed. Debittering of grapefruit juice was evaluated using soluble enzyme, enzyme-free supports, and immobilized catalysts. Enzyme immobilized in BGA reduced naringin and limonin concentrations by 54 and 100%, respectively, while the use of catalyst immobilized in OGA allowed a reduction of 74 and 76%, respectively, obtaining a final concentration of both bitter components under their detection threshold. The use of OGA biocatalyst presented better results than when soluble enzyme or enzyme-free support was utilized. Biocatalyst was successfully applied in juice debittering in five repeated batches.

Asunto(s)

RESUMEN

Some grapefruit juice (GFJ) ingredients and resveratrol, a fruit-derived phytoalexin, are known to inhibit cytochrome P450 (CYP) 2C9. However, their inhibition modes and detailed inhibition kinetics remain undetermined. This study aimed to investigate the inhibitory effects of two GFJ ingredients, bergamottin (BG) and dihydroxybergamottin (DHB), and resveratrol on CYP2C9 activity in vitro. DHB inhibited CYP2C9 activity, as assessed by warfarin 7-hydroxylation, in a preincubation time-dependent manner (i.e., mechanism-based inhibition; MBI), in the same manner as CYP2C19 and CYP3A4. The maximal inactivation rate (kinact,max) was 0.0638 min-1 and 0.12- and 0.26-fold of that for CYP2C19 and CYP3A4, respectively. BG showed both MBI and time-independent competitive inhibition. Resveratrol showed non-competitive inhibition with an inhibition constant (Ki) of 3.64 µM. Unlike the inhibition of CYP2C19 and CYP3A4, resveratrol did not induce MBI. These findings are important for estimating the risk of drug interactions between CYP2C9 substrates and some beverages. (146 words).

Asunto(s)

RESUMEN

The effects of Citri Reticulatae Pericarpium (CRP) and grapefruit juice (GFJ) on the pharmacokinetics of omeprazole were investigated in this study. Sprague-Dawley rats were pretreated with CRP decoction or GFJ for 28 consecutive days. After a single intragastric administration of 6.0 mg/kg, the concentration of omeprazole in the plasma was determined by high-performance liquid chromatography (HPLC), and the pharmacokinetic parameters were calculated by Kinetica software 5.0. A high-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (HPLC-Q-TOF-MS) method was established to identify the chemical components in CRP decoction and GFJ. The results showed that the AUCt-∞ was significantly increased when coadministrated with CRP. The AUC0-t and AUC0-∞ was remarkably increased; the Cl was decreased when coadministrated with GFJ. A total of 31 and 28 bioactive compounds were identified in the CRP decoction and GFJ, respectively. Flavonoids and furanocoumarins, including hesperidin, hesperetin, naringenin, sinensetin, tangeretin, nobiletin, and 6',7'-dihydroxybergamottin, were simultaneously identified in CRP decoction and GFJ. This study indicates that the increased bioavailability of omeprazole may be due to the inhibition of hepatic cytochrome P450 enzymes, and the systemic exposure should be monitored when concomitant administration with CRP and GFJ. PRACTICAL APPLICATIONS: Citri Reticulatae Pericarpium (CRP) has been widely consumed as a daily condiment, functional food, and a traditional Chinese medicine. Omeprazole, primary metabolized by CYP450 enzymes, was usually coadministered with CRP for the treatment of gastrointestinal disease. Studies have confirmed that much fruit juices, including grapefruit juice, may affect drug metabolism enzymes. CRP and grapefruit (Citrus paradisi Macf.) belong to the genus Citrus and family Rutaceae with different species. Therefore, the pharmacokinetic interaction of CRP decoction and grapefruit juice with omeprazole is worthy of attention. The results of this study can provide basic pharmacological data support for the safe and effective clinical use of omeprazole. It can also provide a theoretical basis for the development of new functional products and daily application of CRP.

Asunto(s)

RESUMEN

Organic anion-transporting polypeptides (OATPs) 1A2 and OATP2B1 are expressed in the small intestine and are involved in drug absorption. We identified narirutin, which is present in grapefruit juice, as a novel OATP inhibitor. The citrus fruit jabara also contains high levels of narirutin; therefore, we investigated the inhibitory potency of jabara juice against OATPs. The inhibitory effects of various related compounds on the transport activity of OATPs were evaluated using OATP-expressing HEK293 cells. The IC50 values of narirutin for OATP1A2- and OATP2B1-mediated transport were 22.6 and 18.2 µM, respectively. Other flavanone derivatives from grapefruit juice also inhibited OATP1A2/OATP2B1-mediated transport (order of inhibitory potency: naringenin > narirutin > naringin). Five percent jabara juice significantly inhibited OATP1A2- and OATP2B1-mediated transport by 67 ± 11 and 81 ± 5.5%, respectively (p < 0.05). Based on their inhibitory potency and levels in grapefruit juice, the inhibition of OATPs by grapefruit juice is attributable to both naringin and narirutin. Citrus × jabara, which contains narirutin, potently inhibits OATP-mediated transport.

RESUMEN

Drug-drug interactions (DDI) have been examined for various drugs for oral use, but less for non-oral applications. This study provides DDI prediction methods for non-orally administered CYP3A4 substrates based on clinical DDI data of oral dosages. Gut availability (Fg) and fraction contribution of CYP3A4 to hepatic intrinsic clearance (fmCYP3A4) were predicted by AUC ratio (AUCR) in oral DDI study with/without grapefruit juice, and alteration in intrinsic clearances with/without ketoconazole, respectively. AUCRs of non-orally administered CYP3A4 substrates with/without inhibitors or inducers were predicted with the estimated Fg, fmCYP3A4 and changes in liver CYP3A4 activities with inhibitors/inducers predicted using Simcyp library. DDIs of intravenously administered midazolam and alfentanil with CYP3A4 inhibitors/inducers could be predicted well by this method with predicted AUCRs within ±64% of observed values. Moreover, maximum DDIs with strong CYP3A4 inducers could be predicted by comparing hepatic clearance with hepatic blood flow, as hepatic blood flow indicates the possible maximum hepatic clearance after strong enzyme induction. Predicted AUCRs of midazolam, alfentanil and R- and S-verapamil were less than, but not far from observed ratios, suggesting good conservative prediction. These methods were applied to blonanserin transdermal patch, suggesting much smaller interaction with CYP3A4 inhibitors/inducers compared to oral dosage of blonanserin.

Asunto(s)

RESUMEN

The aim of this study was to examine the preventive action of grapefruit juice (GFJ) against potassium oxonate-induced hyperuricemic mice. The results showed that GFJ significantly (p < .05) inhibit the serum and hepatic xanthine oxidase enzyme, lower uric acid level, serum creatinine, uromodulin, and blood urea nitrogen levels to normal and lower inflammation related genes IL-1ß, caspase-1, NLRP3, and ASC. Furthermore, histopathology analysis revealed that GFJ markedly improve the renal and intestinal morphology. The mRNA expression of urate transporter 1, glucose transporter 9 were downregulated, whereas ATP-binding cassette transporter (ABCG2) was upregulated in the GFJ-treated group. The results of immunohistochemistry revealed that the ABCG2 protein expression in the small and large intestine was significantly upregulated after the GFJ administration. These results suggested that GFJ can be used as a urate lowering agent and future mechanistic studies should be conducted. PRACTICAL APPLICATIONS: The results of current study indicated that utilization of GFJ as an anti-hyperuricemic agent for the treatment of hyperuricemia. This article will be very valuable for all those peoples which are directly or indirectly linked with this disease.

Asunto(s)

RESUMEN

Furanocoumarins are the main compounds responsible for the food-drug interactions known as the grapefruit effect, which is caused by the inhibition of CYP3A4-mediated drug metabolism. We evaluated the effects of two new, low-furanocoumarin grapefruit cultivars on CYP3A4 activity and the roles of different furanocoumarins, individually and together with other juice compounds, in the inhibition of CYP3A4 by grapefruit. Whereas a standard grapefruit cultivar inhibited CYP3A4 activity in a dose-dependent manner, neither of the two examined low-furanocoumarin cultivars had an inhibitory effect. Despite the fact that bergamottin and 6',7'-dihydroxybergamottin are weak inhibitors of CYP3A4, their relatively high levels in grapefruit make them the leading cause of the grapefruit effect. We found that furanocoumarins together with other juice compounds inhibit CYP3A4 in an additive manner. In silico docking simulation was employed, and differentiated between high- and low-potency inhibitors, suggesting that modeling may be useful for identifying potentially harmful food-drug interactions.

Asunto(s)

RESUMEN

OBJECTIVES: Grapefruit (Citrus paradisi) juice enhances the oral bioavailability of drugs that are metabolized by intestinal cytochrome P450 3A4 (CYP3A4). Patients are advised to avoid drinking grapefruit juice to prevent this drug-grapefruit juice interaction. The aim of this study was to investigate whether processing grapefruit juice with cyclodextrins (CDs) would result in preventing or inhibiting this interaction. METHODS: Grapefruit juice and the major furanocoumarins found in grapefruit, bergamottin (BG) and 6', 7'-dihydroxy bergamottin (DHBG) were mixed with α, ß and γCDs. The effects of these processed juice samples and furanocoumarins on CYP3A activity were compared with the corresponding values for unprocessed juices and furanocoumarins. Interactions between CDs and these furanocoumarins were also investigated by phase solubility and 1 H NMR studies. KEY FINDINGS: The inhibition of CYP3A by grapefruit juice was significantly attenuated by processing particularly with γCD. Similar attenuation effects by γCD were observed in the cases of BG and DHBG. Furthermore, BG and DHBG were suggested to be strongly encapsulated in the cavity of γCD. CONCLUSION: The encapsulation of BG and DHBG by γCD and the resulting attenuation of the inhibition of CYP3A activity by grapefruit juice may be applicable to juice processing for preventing drug-grapefruit juice interactions.

Asunto(s)

RESUMEN

Arrhythmogenic ingredients in our diet such as mushrooms, licorice, toxic honey, liquid protein drinks, etc. have long been recognized as rare but important considerations in the differential diagnosis of arrhythmias. Anecdotal reports of torsades de pointes (TdP), arrhythmias and/or sudden death and small studies in normal subjects have suggested that simple ingredients such as grapefruit juice or ingredients in energy drinks marketed as dietary supplements could have direct arrhythmogenic actions, especially in patients with congenital long QT syndrome (cLQTS). Two recent studies that employed the industry-standard "thorough QT" trial design leave no doubt that grapefruit juice and some energy drinks can prolong the QTc interval and to exceed 500 msec. in some patients with cLQTS, a threshold known to signal imminent danger. These reports raise numerous clinically important questions such as which other patients may be at risk of arrhythmias. For example, patients with multiple clinical risk factors for TdP (hypokalemia, bradycardia, female sex, etc.) may be at risk from these and possibly other dietary ingredients ingested by millions of people each day. It is essential that further research evaluate the safety of these and similar food products and that vulnerable patients, especially those with cLQTS, be warned of this serious and emerging threat.

Asunto(s)

RESUMEN

Naringinase is an enzyme complex which exhibits α-l-rhamnosidase and ß-d-glucosidase activity. This enzymatic complex catalyzes the hydrolysis of naringin (4',5,7-trihydroxy flavanone 7-rhamnoglucoside), the main bittering component in grapefruit. Reduction of the level of this substance during the processing of juice has been the focus of many studies. The aim of the study was the immobilization of naringinase on chitosan microspheres activated with glutaraldehyde and, finally, the use of such immobilized enzyme for debittering grapefruit juice. The effect of naringinase concentration and characterization of the immobilized enzyme compared to the soluble enzyme were investigated. The maximum activity was observed at optimum pH 4.0 for both free and immobilized naringinase. However, the optimum temperature was shifted from 70 to 40 °C upon immobilization. The KM value of the immobilized naringinase was higher than that of soluble naringinase. The immobilization did not change the thermal stability of the enzyme. The immobilized naringinase had good operational stability. This preparation retained 88.1 ± 2.8% of its initial activity after ten runs of naringin hydrolysis from fresh grapefruit juice. The results indicate that naringinase immobilized on chitosan has potential applicability for debittering and improving the sensory properties of grapefruit juices.

Asunto(s)

RESUMEN

This study aimed to shed light on the protective and therapeutic anti-osteoporotic effects and mechanisms of action of grapefruit juice (GFJ) on prednisolone-induced osteoporosis a rat femoral fracture model. We found that treating rats with GFJ before and/or after prednisolone-induced osteoporosis resulted in increased bone density, total mineral content, and calcium content to counteract the osteoporotic effects of prednisolone. In parallel, the histological and ultrastructural results of the GFJ-treated groups correlated well with enhanced breaking strength of femurs subjected to a constant load. Furthermore, GFJ treatment before and after prednisolone-induced osteoporosis decreased plasma alkaline phosphatase and tartrate-resistant acid phosphatase activities and increased the level of insulin-like growth factor 1. Mechanistically, our immunohistochemistry study showed that GFJ ameliorated prednisolone-induced osteocalcin depletion, decreased receptor activator of nuclear factor kappa-B ligand (RANKL) expression, and increased osteoprotegerin (OPG) expression. GFJ showed a beneficial anti-osteoporotic effect against prednisolone-induced osteoporosis in rats, possibly via the RANKL/OPG axis, suggesting that GFJ might be a good candidate for developing anti-osteoporotic drugs.

RESUMEN

It has been suggested that the fruit components resveratrol (RSV), 6', 7'-dihydroxybergamottin (DHB), and bergamottin (BG) might inhibit cytochrome P450 2C19 (CYP2C19) activity, but the mode and potency of such inhibition are yet to be investigated. This study aimed to investigate the mode and kinetics of the inhibition of CYP2C19-based omeprazole metabolism by RSV or grapefruit juice components (DHB or BG). RSV and DHB reduced CYP2C19 activity in a preincubation time-dependent manner, suggesting that they inactivated CYP2C19 via mechanism-based inhibition (MBI). Although BG inactivated CYP2C19 in a preincubation time- and concentration-dependent manner, suggesting that both MBI and reversible inhibition contributed to these effects, the concentration required to achieve 50% inhibition was 26-fold higher for reversible inhibition than for MBI (0.859 and 0.0331 µM, respectively), indicating that the inhibition of CYP2C19 by BG is primarily attributable to MBI. Based on the estimated intestinal concentrations of these components, it is considered that >90% of CYP2C19 would be inactivated after the consumption of normal amounts of grapefruit juice or RSV-containing substances. In conclusion, these findings suggest that food containing these components has the potential to evoke drug-food interactions caused by the MBI of intestinal CYP2C19 activity in the clinical setting.

Asunto(s)

RESUMEN

4ß-Hydroxycholesterol (4ßOHC) is an endogenous CYP3A4 metabolite. However, it is unclear whether circulating levels of 4ßOHC may reflect hepatic CYP3A4 activity or both hepatic and intestinal enzyme activity. The aim of this study was to investigate the effect of grapefruit juice, regarded to be a selective intestinal CYP3A4 inhibitor, on serum 4ßOHC levels in healthy volunteers. The participants (n = 22) consumed grapefruit juice twice daily for 3 weeks followed by a 2-week washout period. Blood samples for measurements of 4ßOHC and the non-CYP3A4-derived oxysterols 24-hydroxycholesterol (24OHC) and 27-hydroxycholesterol (27OHC), as well as lathosterol and total cholesterol, were drawn on days 0, 7, 21, and 35. Median individual changes (ratios) in cholesterol-corrected 4ßOHC levels from baseline to weeks 1, 3, and 5 were 0.94 (P = 0.2), 0.98 (P = 0.3), and 0.97 (P = 0.9), respectively. In comparison, median changes (ratios) in cholesterol-corrected levels of 24OHC at the same points were 1.01 (P = 0.6), 0.98 (P = 0.3), and 0.99 (P = 0.5), and of 27OHC 1.01 (P = 0.8), 0.97 (P = 0.5), and 0.99 (P = 0.2). Surprisingly, serum concentration of cholesterol was significantly reduced by approximately 5% after 1 week (P = 0.03), while median cholesterol-corrected levels of lathosterol increased significantly and persistently by approximately 15% during the whole 5-week period (P < 0.04). In conclusion, the present findings suggest that intestinal CYP3A4 is not relevant for the overall formation of 4ßOHC in healthy volunteers. The fact that grapefruit juice altered cholesterol homeostasis should be further investigated.

Asunto(s)